MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cell Metabolism' source. Tue, 07 Feb 2012 08:48:53 +0100 http://www.medworm.com/index.php?rid=5659174&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285542%26dopt%3DAbstract Authors: Coupé B, Ishii Y, Dietrich MO, Komatsu M, Horvath TL, Bouret SG Abstract The hypothalamic melanocortin system, which includes neurons that produce pro-opiomelanocortin (POMC)-derived peptides, is a major negative regulator of energy balance. POMC neurons begin to acquire their unique properties during neonatal life. The formation of functional neural systems requires massive cytoplasmic remodeling that may involve autophagy, an important intracellular mechanism for the degradation of damaged proteins and organelles. Here we investigated the functional and structural effects of the deletion of an essential autophagy gene, Atg7, in POMC neurons. Lack of Atg7 in POMC neurons caused higher postweaning body weight, increased adiposity, and glucose intolerance. These metabolic ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5659174 Tue, 24 Jan 2012 05:00:00 +0100 5659174 http://www.medworm.com/index.php?rid=5623451&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22244528%26dopt%3DAbstract Authors: Ryan KK, Woods SC, Seeley RJ Abstract The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the thresh... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5623451 Wed, 11 Jan 2012 05:00:00 +0100 5623451 http://www.medworm.com/index.php?rid=5623450&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245570%26dopt%3DAbstract Authors: Zhang C, Forlano PM, Cone RD Abstract Plasticity in growth and reproductive behavior is found in many vertebrate species, but is common in male teleost fish. Typically, "bourgeois" males are considerably larger and defend breeding territories while "parasitic" variants are small and use opportunistic breeding strategies. The P locus mediates this phenotypic variation in Xiphophorus and encodes variant alleles of the melanocortin-4 receptor (MC4R). However, deletion of the MC4R has modest effects on somatic growth and reproduction in mammals, suggesting a fundamental difference in the neuroendocrine function of central melanocortin signaling in teleosts. Here we show in a teleost that the hypothalamic pro-opiomelanocortin and AgRP neurons are hypophysiotropic, projecting t... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5623450 Wed, 11 Jan 2012 05:00:00 +0100 5623450 http://www.medworm.com/index.php?rid=5578620&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225867%26dopt%3DAbstract Authors: Seeley RJ Abstract Expanding adipose tissue in obesity requires a great deal of angiogenesis to support increasing volumes of tissue. A growing body of evidence indicates that inhibiting these blood vessels can result in substantial weight loss, and now this has been demonstrated in nonhuman primates. PMID: 22225867 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578620 Wed, 04 Jan 2012 05:00:00 +0100 5578620 http://www.medworm.com/index.php?rid=5578619&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225868%26dopt%3DAbstract Authors: Garrison BS, Rossi DJ Abstract While age-dependent stem cell decline is widely recognized as being a key component of organismal aging, the underlying mechanisms remain elusive. In this issue of Cell Metabolism, Suomalainen and colleagues provide evidence that mitochondrial mutation and associated reactive oxygen species can adversely impact tissue-specific stem and progenitor cell function. PMID: 22225868 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578619 Wed, 04 Jan 2012 05:00:00 +0100 5578619 http://www.medworm.com/index.php?rid=5578618&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225869%26dopt%3DAbstract Power Surge: Supporting Cells "Fuel" Cancer Cell Mitochondria. Cell Metab. 2012 Jan 4;15(1):4-5 Authors: Martinez-Outschoorn UE, Sotgia F, Lisanti MP Abstract An emerging paradigm in tumor metabolism is that catabolism in host cells "fuels" the anabolic growth of cancer cells via energy transfer. A study in Nature Medicine (Nieman et al., 2011) supports this; they show that triglyceride catabolism in adipocytes drives ovarian cancer metastasis by providing fatty acids as mitochondrial fuels. PMID: 22225869 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578618 Wed, 04 Jan 2012 05:00:00 +0100 5578618 http://www.medworm.com/index.php?rid=5578617&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225870%26dopt%3DAbstract Authors: Berger SL Abstract Transgenerational inheritance of epigenetic characteristics in plants has been reported, whereas nongenetic persistence of complex phenotypes in animals is controversial. A recent report by Anne Brunet and colleagues describes a fascinating example of persistence across generations of extended life span in worm and explores whether epigenetic mechanisms account for the longevity. PMID: 22225870 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578617 Wed, 04 Jan 2012 05:00:00 +0100 5578617 http://www.medworm.com/index.php?rid=5578616&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225871%26dopt%3DAbstract Authors: Allen TL, Whitham M, Febbraio MA Abstract The role of the cytokine interleukin-6 (IL-6) in metabolic homeostasis is the subject of conjecture. Recent work in Nature Medicine (Ellingsgaard et al., 2011) demonstrates that IL-6 released from skeletal muscle during exercise mediates crosstalk between insulin-sensitive tissues, intestinal L cells, and pancreatic islets to adapt to changes in insulin demand. PMID: 22225871 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578616 Wed, 04 Jan 2012 05:00:00 +0100 5578616 http://www.medworm.com/index.php?rid=5578615&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225872%26dopt%3DAbstract Authors: Stienstra R, Tack CJ, Kanneganti TD, Joosten LA, Netea MG Abstract Obesity-induced inflammation is an important contributor to the induction of insulin resistance. Recently, the cytokine interleukin-1β (IL-1β) has emerged as a prominent instigator of the proinflammatory response in obesity. Several studies over the last year have subsequently deciphered the molecular mechanisms responsible for IL-1β activation in adipose tissue, liver, and macrophages and demonstrated a central role of the processing enzyme caspase-1 and of the protein complex leading to its activation called the inflammasome. These data suggest that activation of the inflammasome represents a crucial step in the road from obesity to insulin resistance and type 2 diabetes. PMID: 22225872 [PubMed - i... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578615 Wed, 04 Jan 2012 05:00:00 +0100 5578615 http://www.medworm.com/index.php?rid=5578614&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225873%26dopt%3DAbstract Metabolic disease drug discovery- "hitting the target" is easier said than done. Cell Metab. 2012 Jan 4;15(1):19-24 Authors: Moller DE Abstract Despite the advent of new drug classes, the global epidemic of cardiometabolic disease has not abated. Continuing unmet medical needs remain a major driver for new research. Drug discovery approaches in this field have mirrored industry trends, leading to a recent increase in the number of molecules entering development. However, worrisome trends and newer hurdles are also apparent. The history of two newer drug classes-glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors-illustrates both progress and challenges. Future success requires that researchers learn from these experiences and continue to explore ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578614 Wed, 04 Jan 2012 05:00:00 +0100 5578614 http://www.medworm.com/index.php?rid=5578613&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225874%26dopt%3DAbstract Authors: Guerci A, Lahoute C, Hébrard S, Collard L, Graindorge D, Favier M, Cagnard N, Batonnet-Pichon S, Précigout G, Garcia L, Tuil D, Daegelen D, Sotiropoulos A Abstract Adult skeletal muscles adapt their fiber size to workload. We show that serum response factor (Srf) is required for satellite cell-mediated hypertrophic muscle growth. Deletion of Srf from myofibers and not satellite cells blunts overload-induced hypertrophy, and impairs satellite cell proliferation and recruitment to pre-existing fibers. We reveal a gene network in which Srf within myofibers modulates interleukin-6 and cyclooxygenase-2/interleukin-4 expressions and therefore exerts a paracrine control of satellite cell functions. In Srf-deleted muscles, in vivo overexpression of interleukin-6 is sufficient t... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578613 Wed, 04 Jan 2012 05:00:00 +0100 5578613 http://www.medworm.com/index.php?rid=5578612&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225875%26dopt%3DAbstract Authors: Matsubara T, Mita A, Minami K, Hosooka T, Kitazawa S, Takahashi K, Tamori Y, Yokoi N, Watanabe M, Matsuo E, Nishimura O, Seino S Abstract Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn(-/-)) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578612 Wed, 04 Jan 2012 05:00:00 +0100 5578612 http://www.medworm.com/index.php?rid=5578611&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225876%26dopt%3DAbstract Authors: Shimizu I, Yoshida Y, Katsuno T, Tateno K, Okada S, Moriya J, Yokoyama M, Nojima A, Ito T, Zechner R, Komuro I, Kobayashi Y, Minamino T Abstract Several clinical studies have shown that insulin resistance is prevalent among patients with heart failure, but the underlying mechanisms have not been fully elucidated. Here, we report a mechanism of insulin resistance associated with heart failure that involves upregulation of p53 in adipose tissue. We found that pressure overload markedly upregulated p53 expression in adipose tissue along with an increase of adipose tissue inflammation. Chronic pressure overload accelerated lipolysis in adipose tissue. In the presence of pressure overload, inhibition of lipolysis by sympathetic denervation significantly downregulated adipose p... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578611 Wed, 04 Jan 2012 05:00:00 +0100 5578611 http://www.medworm.com/index.php?rid=5578610&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225877%26dopt%3DAbstract Authors: Zhang T, Wang S, Lin Y, Xu W, Ye D, Xiong Y, Zhao S, Guan KL Abstract Glycogen phosphorylase (GP) catalyzes the rate-limiting step in glycogen catabolism and plays a key role in maintaining cellular and organismal glucose homeostasis. GP is the first protein whose function was discovered to be regulated by reversible protein phosphorylation, which is controlled by phosphorylase kinase (PhK) and protein phosphatase 1 (PP1). Here we report that lysine acetylation negatively regulates GP activity by both inhibiting enzyme activity directly and promoting dephosphorylation. Acetylation of GP Lys(470) enhances its interaction with the PP1 substrate-targeting subunit, G(L), and PP1, thereby promoting GP dephosphorylation and inactivation. We show that GP acetylation is stimulate... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578610 Wed, 04 Jan 2012 05:00:00 +0100 5578610 http://www.medworm.com/index.php?rid=5578609&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225878%26dopt%3DAbstract Authors: Roh HC, Collier S, Guthrie J, Robertson JD, Kornfeld K Abstract Zinc is an essential trace element involved in many biological processes and human diseases. Because zinc deficiency and excess are deleterious, animals require homeostatic mechanisms to maintain zinc levels in response to dietary fluctuations. Here, we demonstrate that lysosome-related organelles in intestinal cells of C. elegans, called gut granules, function as the major site of zinc storage. Zinc storage in gut granules promotes detoxification and subsequent mobilization, linking cellular and organismal zinc metabolism. The cation diffusion facilitator protein CDF-2 plays a critical role in this process by transporting zinc into gut granules. In response to high dietary zinc, gut granules displayed struct... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578609 Wed, 04 Jan 2012 05:00:00 +0100 5578609 http://www.medworm.com/index.php?rid=5578608&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225879%26dopt%3DAbstract Authors: Ahlqvist KJ, Hämäläinen RH, Yatsuga S, Uutela M, Terzioglu M, Götz A, Forsström S, Salven P, Angers-Loustau A, Kopra OH, Tyynismaa H, Larsson NG, Wartiovaara K, Prolla T, Trifunovic A, Suomalainen A Abstract Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatm... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578608 Wed, 04 Jan 2012 05:00:00 +0100 5578608 http://www.medworm.com/index.php?rid=5578607&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22225880%26dopt%3DAbstract Authors: Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, Dang CV Abstract Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using stable isotope-resolved metabolomics. Using [U-(13)C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-(13)C,(15)N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5578607 Wed, 04 Jan 2012 05:00:00 +0100 5578607 http://www.medworm.com/index.php?rid=5550489&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197324%26dopt%3DAbstract Authors: Sieber MH, Thummel CS Abstract Although transintestinal cholesterol efflux has been identified as an important means of clearing excess sterols, the mechanisms that underlie this process remain poorly understood. Here, we show that magro, a direct target of the Drosophila DHR96 nuclear receptor, is required in the intestine to maintain cholesterol homeostasis. magro encodes a LipA homolog that is secreted from the anterior gut into the intestinal lumen to digest dietary triacylglycerol. Expression of magro in intestinal cells is required to hydrolyze cholesterol esters and promote cholesterol clearance. Restoring magro expression in the intestine of DHR96 mutants rescues their defects in triacylglycerol and cholesterol metabolism. These studies show that the central role o... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5550489 Thu, 22 Dec 2011 05:00:00 +0100 5550489 http://www.medworm.com/index.php?rid=5550488&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197325%26dopt%3DAbstract Authors: Haeusler RA, Pratt-Hyatt M, Welch CL, Klaassen CD, Accili D Abstract The association of type 2 diabetes with elevated plasma triglyceride (TG) and very low-density lipoproteins (VLDL), and intrahepatic lipid accumulation represents a pathophysiological enigma and an unmet therapeutic challenge. Here, we uncover a link between insulin action through FoxO1, bile acid (BA) composition, and altered lipid homeostasis that brings new insight to this longstanding conundrum. FoxO1 ablation brings about two signature lipid abnormalities of diabetes and the metabolic syndrome, elevated liver and plasma TG. These changes are associated with deficiency of 12α-hydroxylated BAs and their synthetic enzyme, Cyp8b1, that hinders the TG-lowering effects of the BA receptor, Fxr. Accordingly... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5550488 Thu, 22 Dec 2011 05:00:00 +0100 5550488 http://www.medworm.com/index.php?rid=5535554&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100406%26dopt%3DAbstract Authors: Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordóñez A, Corral-Escariz M, Soro I, López-Bernardo E, Perales-Clemente E, Martínez-Ruiz A, Enríquez JA, Aragonés J, Cadenas S, Landázuri MO Abstract The fine regulation of mitochondrial function has proved to be an essential metabolic adaptation to fluctuations in oxygen availability. During hypoxia, cells activate an anaerobic switch that favors glycolysis and attenuates the mitochondrial activity. This switch involves the hypoxia-inducible transcription factor-1 (HIF-1). We have identified a HIF-1 target gene, the mitochondrial NDUFA4L2 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2). Our results, obtained employing NDUFA4L2-silenced cells and NDUFA4L2 knockout murine embryonic fibrob... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535554 Wed, 07 Dec 2011 05:00:00 +0100 5535554 http://www.medworm.com/index.php?rid=5535553&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100407%26dopt%3DAbstract Authors: Vella KR, Ramadoss P, Lam FS, Harris JC, Ye FD, Same PD, O'Neill NF, Maratos-Flier E, Hollenberg AN Abstract Fasting-induced suppression of the hypothalamic-pituitary-thyroid (HPT) axis is an adaptive response to decrease energy expenditure during food deprivation. Previous studies demonstrate that leptin communicates nutritional status to the HPT axis through thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus. Leptin targets TRH neurons either directly or indirectly via the arcuate nucleus through pro-opiomelanocortin (POMC) and agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons. To evaluate the role of these pathways in vivo, we developed double knockout mice that lack both the melanocortin 4 receptor (MC4R) and NPY. We sh... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535553 Wed, 07 Dec 2011 05:00:00 +0100 5535553 http://www.medworm.com/index.php?rid=5535552&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100408%26dopt%3DAbstract Authors: Hirschey MD Abstract Seven mammalian sirtuins are nicotinamide adenine dinucleotide (NAD)(+)-dependent deacetylases and are important modulators of energy metabolism and stress resistance. Two new studies by Du et al. (2011) and Peng et al. (2011) identify a new enzymatic activity for SIRT5, expanding the cellular repertoire of posttranslational modifications targeted by the sirtuins. PMID: 22100408 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535552 Wed, 07 Dec 2011 05:00:00 +0100 5535552 http://www.medworm.com/index.php?rid=5535551&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100409%26dopt%3DAbstract Authors: Albrecht SC, Barata AG, Großhans J, Teleman AA, Dick TP Abstract The glutathione redox couple (GSH/GSSG) and hydrogen peroxide (H(2)O(2)) are central to redox homeostasis and redox signaling, yet their distribution within an organism is difficult to measure. Using genetically encoded redox probes in Drosophila, we establish quantitative in vivo mapping of the glutathione redox potential (E(GSH)) and H(2)O(2) in defined subcellular compartments (cytosol and mitochondria) across the whole animal during development and aging. A chemical strategy to trap the in vivo redox state of the transgenic biosensor during specimen dissection and fixation expands the scope of fluorescence redox imaging to include the deep tissues of the adult fly. We find that development and aging ar... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535551 Wed, 07 Dec 2011 05:00:00 +0100 5535551 http://www.medworm.com/index.php?rid=5535550&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152297%26dopt%3DAbstract Authors: Djouadi F, Bastin J PMID: 22152297 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535550 Wed, 07 Dec 2011 05:00:00 +0100 5535550 http://www.medworm.com/index.php?rid=5535549&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152298%26dopt%3DAbstract Authors: Viscomi C, Zeviani M PMID: 22152298 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535549 Wed, 07 Dec 2011 05:00:00 +0100 5535549 http://www.medworm.com/index.php?rid=5535548&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152299%26dopt%3DAbstract Authors: Tormos KV, Chandel NS Abstract Reactive oxygen species (ROS) dictate biological outcomes and are linked with myriad pathologies. However, measuring ROS in vivo remains a major obstacle in the field. Here, Albrecht et al. (2011) demonstrate the efficacy of redox-sensitive GFP in measuring glutathione redox state and H(2)O(2) levels of tissues in Drosophila. PMID: 22152299 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535548 Wed, 07 Dec 2011 05:00:00 +0100 5535548 http://www.medworm.com/index.php?rid=5535547&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152300%26dopt%3DAbstract Authors: Wan M, Birnbaum MJ Abstract The serine-threonine protein kinase Akt2, also known as PKBβ, has been shown to regulate glucose and lipid metabolism in animal models. In a recent study published in Science, Hussain et al. (2011) report that in human subjects an activating mutation of Akt2 leads to hypoglycemia and, unexpectedly, asymmetric overgrowth. PMID: 22152300 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535547 Wed, 07 Dec 2011 05:00:00 +0100 5535547 http://www.medworm.com/index.php?rid=5535546&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152301%26dopt%3DAbstract Authors: Bélanger M, Allaman I, Magistretti PJ Abstract The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. PMID: 22152301 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535546 Wed, 07 Dec 2011 05:00:00 +0100 5535546 http://www.medworm.com/index.php?rid=5535545&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152302%26dopt%3DAbstract Authors: Gupta RK, Rosen ED, Spiegelman BM Abstract The investigation of metabolic regulation at the transcriptional level presents different challenges than those encountered in the study of other important problems like development or cancer. Levels of key components like glucose, insulin, and lipids can be modulated but rarely change in an all-or-none fashion, necessitating quantitative techniques that can be applied to multiple tissues and systems. This review examines recent advances in methods for studying transcriptional regulation, with special emphasis on metabolic science. We compare these methods for investigators trying to decide on the best approach for their particular physiological paradigm or model system. PMID: 22152302 [PubMed - in process] (Source: Cell Metab... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535545 Wed, 07 Dec 2011 05:00:00 +0100 5535545 http://www.medworm.com/index.php?rid=5535544&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152303%26dopt%3DAbstract Authors: Pols TW, Nomura M, Harach T, Lo Sasso G, Oosterveer MH, Thomas C, Rizzo G, Gioiello A, Adorini L, Pellicciari R, Auwerx J, Schoonjans K Abstract The G protein-coupled receptor TGR5 has been identified as an important component of the bile acid signaling network, and its activation has been linked to enhanced energy expenditure and improved glycemic control. Here, we demonstrate that activation of TGR5 in macrophages by 6α-ethyl-23(S)-methylcholic acid (6-EMCA, INT-777), a semisynthetic BA, inhibits proinflammatory cytokine production, an effect mediated by TGR5-induced cAMP signaling and subsequent NF-κB inhibition. TGR5 activation attenuated atherosclerosis in Ldlr(-/-)Tgr5(+/+) mice but not in Ldlr(-/-)Tgr5(-/-) double-knockout mice. The inhibition of lesion formation ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535544 Wed, 07 Dec 2011 05:00:00 +0100 5535544 http://www.medworm.com/index.php?rid=5535543&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152304%26dopt%3DAbstract Authors: Warne JP, Alemi F, Reed AS, Varonin JM, Chan H, Piper ML, Mullin ME, Myers MG, Corvera CU, Xu AW Abstract Hepatic steatosis is generally thought to develop via peripheral mechanisms associated with obesity. We show that chronic central infusion of leptin suppresses hepatic lipogenic gene expression and reduces triglyceride content via stimulation of hepatic sympathetic activity. This leptin function is independent of feeding and body weight but requires phosphatidylinositol 3-kinase (PI3K) signaling. Attenuation of leptin-induced PI3K signaling, brought about by transgenic expression of phosphatase and tensin homolog (PTEN) in leptin receptor neurons, leads to decreased hepatic sympathetic tone and increased triglyceride levels without affecting adiposity or hepatic insuli... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535543 Wed, 07 Dec 2011 05:00:00 +0100 5535543 http://www.medworm.com/index.php?rid=5535542&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152305%26dopt%3DAbstract This study tested whether humans with NAFLD have abnormal in vivo hepatic mitochondrial metabolism. Subjects with low (3.0%) and high (17%) intrahepatic triglyceride (IHTG) were studied using (2)H and (13)C tracers to evaluate systemic lipolysis, hepatic glucose production, and mitochondrial pathways (TCA cycle, anaplerosis, and ketogenesis). Individuals with NAFLD had 50% higher rates of lipolysis and 30% higher rates of gluconeogenesis. There was a positive correlation between IHTG content and both mitochondrial oxidative and anaplerotic fluxes. These data indicate that mitochondrial oxidative metabolism is ∼2-fold greater in those with NAFLD, providing a potential link between IHTG content, oxidative stress, and liver damage. PMID: 22152305 [PubMed - in process] (Source: Cell Met... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535542 Wed, 07 Dec 2011 05:00:00 +0100 5535542 http://www.medworm.com/index.php?rid=5535541&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22152306%26dopt%3DAbstract Authors: Holleboom AG, Karlsson H, Lin RS, Beres TM, Sierts JA, Herman DS, Stroes ES, Aerts JM, Kastelein JJ, Motazacker MM, Dallinga-Thie GM, Levels JH, Zwinderman AH, Seidman JG, Seidman CE, Ljunggren S, Lefeber DJ, Morava E, Wevers RA, Fritz TA, Tabak LA, Lindahl M, Hovingh GK, Kuivenhoven JA Abstract Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attribut... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5535541 Wed, 07 Dec 2011 05:00:00 +0100 5535541 http://www.medworm.com/index.php?rid=5421907&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078933%26dopt%3DAbstract Authors: Qiang L, Lin HV, Kim-Muller JY, Welch CL, Gu W, Accili D Abstract Dyslipidemia and atherosclerosis are associated with reduced insulin sensitivity and diabetes, but the mechanism is unclear. Gain of function of the gene encoding deacetylase SirT1 improves insulin sensitivity and could be expected to protect against lipid abnormalities. Surprisingly, when transgenic mice overexpressing SirT1 (SirBACO) are placed on atherogenic diet, they maintain better glucose homeostasis, but develop worse lipid profiles and larger atherosclerotic lesions than controls. We show that transcription factor cAMP response element binding protein (Creb) is deacetylated in SirBACO mice. We identify Lys136 is a substrate for SirT1-dependent deacetylation that affects Creb activity by preventing i... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421907 Wed, 09 Nov 2011 05:00:00 +0100 5421907 http://www.medworm.com/index.php?rid=5421916&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055498%26dopt%3DAbstract Authors: Langin D Abstract Adipose tissue is the main site of storage and mobilization of lipid. In a recent study published in Nature, Arner et al. (2011) report that high storage and low removal of adipose triglycerides promotes obesity, whereas low storage and low removal favor the development of dyslipidemia in humans. PMID: 22055498 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421916 Wed, 02 Nov 2011 04:00:00 +0100 5421916 http://www.medworm.com/index.php?rid=5421915&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055499%26dopt%3DAbstract Authors: Zhou Y, Lu T, Xie T Abstract PGC-1 regulates energy homeostasis and mitochondrial activity. In this issue, Rera et al. (2011) show that dPGC-1 overexpression in Drosophila intestinal stem cells and their immediate progeny extends organismal life span and protects against age-related loss of intestinal homeostasis and integrity, thereby establishing a link between mitochondria, tissue stem cells, and aging. PMID: 22055499 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421915 Wed, 02 Nov 2011 04:00:00 +0100 5421915 http://www.medworm.com/index.php?rid=5421914&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055500%26dopt%3DAbstract Authors: Rochford JJ, Myers MG, Heisler LK Abstract The brain melanocortin system is a primary gateway through which energy balance is controlled. Diano and colleagues report a novel cellular mechanism mediated via reactive oxygen species (ROS) that regulates the activity of these melanocortin neurons in response to energy status, thereby modulating appetitive behavior (Diano et al., 2011). PMID: 22055500 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421914 Wed, 02 Nov 2011 04:00:00 +0100 5421914 http://www.medworm.com/index.php?rid=5421913&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055501%26dopt%3DAbstract Authors: Bornfeldt KE, Tabas I Abstract Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role of hyperglycemia in CAD associated with type 2 diabetes is less clear. Understanding the mechanisms whereby type 2 diabetes exacerbates CAD offers hope for new therapeutic strategies to prevent and treat atherosclerotic vascular disease. PMID: 22055501... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421913 Wed, 02 Nov 2011 04:00:00 +0100 5421913 http://www.medworm.com/index.php?rid=5421912&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055502%26dopt%3DAbstract Authors: Banks AS, Kim-Muller JY, Mastracci TL, Kofler NM, Qiang L, Haeusler RA, Jurczak MJ, Laznik D, Heinrich G, Samuel VT, Shulman GI, Papaioannou VE, Accili D Abstract FoxO1 integrates multiple metabolic pathways. Nutrient levels modulate FoxO1 acetylation, but the functional consequences of this posttranslational modification are unclear. To answer this question, we generated mice bearing alleles that encode constitutively acetylated and acetylation-defective FoxO1 proteins. Homozygosity for an allele mimicking constitutive acetylation (Foxo1(KQ/KQ)) results in embryonic lethality due to cardiac and angiogenesis defects. In contrast, mice homozygous for a constitutively deacetylated Foxo1 allele (Foxo1(KR/KR)) display a unique metabolic phenotype of impaired insulin action on... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421912 Wed, 02 Nov 2011 04:00:00 +0100 5421912 http://www.medworm.com/index.php?rid=5421911&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055503%26dopt%3DAbstract Authors: Oka S, Alcendor R, Zhai P, Park JY, Shao D, Cho J, Yamamoto T, Tian B, Sadoshima J Abstract High energy production in mitochondria is essential for maintaining cardiac contraction in the heart. Genes regulating mitochondrial function are commonly downregulated during heart failure. Here we show that both PPARα and Sirt1 are upregulated by pressure overload in the heart. Haploinsufficiency of either PPARα or Sirt1 attenuated pressure overload-induced cardiac hypertrophy and failure, whereas simultaneous upregulation of PPARα and Sirt1 exacerbated the cardiac dysfunction. PPARα and Sirt1 coordinately suppressed genes involved in mitochondrial function that are regulated by estrogen-related receptors (ERRs). PPARα bound and recruited Sirt1 to the ERR response element (ER... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421911 Wed, 02 Nov 2011 04:00:00 +0100 5421911 http://www.medworm.com/index.php?rid=5421910&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055504%26dopt%3DAbstract In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. PMID: 22055504 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421910 Wed, 02 Nov 2011 04:00:00 +0100 5421910 http://www.medworm.com/index.php?rid=5421909&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055505%26dopt%3DAbstract Authors: Rera M, Bahadorani S, Cho J, Koehler CL, Ulgherait M, Hur JH, Ansari WS, Lo T, Jones DL, Walker DW Abstract In mammals, the PGC-1 transcriptional coactivators are key regulators of energy metabolism, including mitochondrial biogenesis and respiration, which have been implicated in numerous pathogenic conditions, including neurodegeneration and cardiomyopathy. Here, we show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondrial activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421909 Wed, 02 Nov 2011 04:00:00 +0100 5421909 http://www.medworm.com/index.php?rid=5421908&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055506%26dopt%3DAbstract Authors: Nandal A, Ruiz JC, Subramanian P, Ghimire-Rijal S, Sinnamon RA, Stemmler TL, Bruick RK, Philpott CC Abstract Mammalian cells express dozens of iron-containing proteins, yet little is known about the mechanism of metal ligand incorporation. Human poly (rC) binding protein 1 (PCBP1) is an iron chaperone that binds iron and delivers it to ferritin, a cytosolic iron storage protein. We have identified the iron-dependent prolyl hydroxylases (PHDs) and asparaginyl hydroxylase (FIH1) that modify hypoxia-inducible factor α (HIFα) as targets of PCBP1. Depletion of PCBP1 or PCBP2 in cells led to loss of PHD activity, manifested by reduced prolyl hydroxylation of HIF1α, impaired degradation of HIF1α through the VHL/proteasome pathway, and accumulation of active HIF1 transcription... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5421908 Wed, 02 Nov 2011 04:00:00 +0100 5421908 http://www.medworm.com/index.php?rid=5380239&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019086%26dopt%3DAbstract Authors: Mayer FV, Heath R, Underwood E, Sanders MJ, Carmena D, McCartney RR, Leiper FC, Xiao B, Jing C, Walker PA, Haire LF, Ogrodowicz R, Martin SR, Schmidt MC, Gamblin SJ, Carling D Abstract The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5380239 Wed, 19 Oct 2011 04:00:00 +0100 5380239 http://www.medworm.com/index.php?rid=5380240&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22019085%26dopt%3DAbstract Authors: De Domenico I, Lo E, Yang B, Korolnek T, Hamza I, Ward DM, Kaplan J Abstract The iron exporter ferroportin (Fpn) is essential to transfer iron from cells to plasma. Systemic iron homeostasis in vertebrates is regulated by the hepcidin-mediated internalization of Fpn. Here, we demonstrate a second route for Fpn internalization; when cytosolic iron levels are low, Fpn is internalized in a hepcidin-independent manner dependent upon the E3 ubiquitin ligase Nedd4-2 and the Nedd4-2 binding protein Nfdip-1. Retention of cell-surface Fpn through reductions in Nedd4-2 results in cell death through depletion of cytosolic iron. Nedd4-2 is also required for internalization of Fpn in the absence of ferroxidase activity as well as for the entry of hepcidin-induced Fpn into the multives... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5380240 Tue, 18 Oct 2011 04:00:00 +0100 5380240 http://www.medworm.com/index.php?rid=5380242&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000926%26dopt%3DAbstract Authors: Loh K, Fukushima A, Zhang X, Galic S, Briggs D, Enriori PJ, Simonds S, Wiede F, Reichenbach A, Hauser C, Sims NA, Bence KK, Zhang S, Zhang ZY, Kahn BB, Neel BG, Andrews ZB, Cowley MA, Tiganis T Abstract In obesity, anorectic responses to leptin are diminished, giving rise to the concept of "leptin resistance." Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high-fat-diet-induced weight gain and the development of... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5380242 Tue, 11 Oct 2011 04:00:00 +0100 5380242 http://www.medworm.com/index.php?rid=5380241&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000927%26dopt%3DAbstract Authors: De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, Ghatei MA, Bloom SR, Matthews PM, Beaver JD, Dhillo WS Abstract Obesity is a major public health issue worldwide. Understanding how the brain controls appetite offers promising inroads toward new therapies for obesity. Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are coreleased postprandially and reduce appetite and inhibit food intake when administered to humans. However, the effects of GLP-1 and the ways in which PYY and GLP-1 act together to modulate brain activity in humans are unknown. Here, we have used functional MRI to determine these effects in healthy, normal-weight human subjects and compared them to those seen physiologically following a meal. We provide a demonstration that the combine... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5380241 Tue, 11 Oct 2011 04:00:00 +0100 5380241 http://www.medworm.com/index.php?rid=5313304&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982701%26dopt%3DAbstract Authors: Hart-Unger S, Korach KS Abstract Estrogens have preventative effects on weight gain and associated comorbidities, but the tissue-specific targets remain unknown. Here, Xu et al. (2011) demonstrate that ablation of estrogen signaling in two populations of hypothalamic neurons leads to weight gain and subsequent metabolic dysregulation and could be important target sites of estrogen actions. PMID: 21982701 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313304 Wed, 05 Oct 2011 04:00:00 +0100 5313304 http://www.medworm.com/index.php?rid=5313303&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982702%26dopt%3DAbstract Authors: Brasaemle DL Abstract Phospholipids provide an amphipathic barrier between lipid droplets and the cytoplasm of cells. In this issue of Cell Metabolism, Krahmer and colleagues (2011) define a role for phosphatidylcholine in preventing lipid droplet coalescence and show that the rate-limiting enzyme in phosphatidylcholine synthesis is activated through binding to lipid droplets. PMID: 21982702 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313303 Wed, 05 Oct 2011 04:00:00 +0100 5313303 http://www.medworm.com/index.php?rid=5313302&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982703%26dopt%3DAbstract Authors: Thorens B Abstract The molecular mechanisms linking diet, obesity, and type 2 diabetes are still poorly understood. In a recent paper, Ohtsubo et al. (2011) show that high lipid levels induce nuclear exclusion of Foxa2 and HNF1α in β cells, leading to impaired expression and glycosylation of proteins controlling glucose-stimulated insulin secretion. PMID: 21982703 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313302 Wed, 05 Oct 2011 04:00:00 +0100 5313302 http://www.medworm.com/index.php?rid=5313301&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982704%26dopt%3DAbstract Authors: Seale P Abstract Brown adipocytes burn chemical energy to produce heat for protection against hypothermia and obesity. Sellayah et al. now reveal that a secreted neuropeptide, Orexin, functions a key driver of brown adipocyte differentiation through direct actions on brown adipose precursors. PMID: 21982704 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313301 Wed, 05 Oct 2011 04:00:00 +0100 5313301 http://www.medworm.com/index.php?rid=5313300&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982705%26dopt%3DAbstract Authors: Locasale JW, Cantley LC Abstract The study of normal mammalian cell growth and the defects that contribute to disease pathogenesis links metabolism to cell growth. Here, we visit several aspects of growth-promoting metabolism, emphasizing recent advances in our understanding of how alterations in glucose metabolism affect cytosolic and mitochondrial redox potential and ATP generation. These alterations drive cell proliferation not only through supporting biosynthesis, energy metabolism, and maintaining redox potential but also through initiating signaling mechanisms that are still poorly characterized. The evolutionary basis of these additional layers of growth control is also discussed. PMID: 21982705 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313300 Wed, 05 Oct 2011 04:00:00 +0100 5313300 http://www.medworm.com/index.php?rid=5313299&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982706%26dopt%3DAbstract Authors: Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, Zhang X, Zou F, Gent LM, Hahner LD, Khan SA, Elias CF, Elmquist JK, Clegg DJ Abstract Estrogens regulate body weight and reproduction primarily through actions on estrogen receptor-α (ERα). However, ERα-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERα in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERα in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERα in hypothalamic pro-opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or f... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313299 Wed, 05 Oct 2011 04:00:00 +0100 5313299 http://www.medworm.com/index.php?rid=5313298&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982707%26dopt%3DAbstract This study defined Inpp4b as a major modulator of the osteoclast differentiation and as a gene linked to variability of bone mineral density in mice and humans. PMID: 21982707 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313298 Wed, 05 Oct 2011 04:00:00 +0100 5313298 http://www.medworm.com/index.php?rid=5313297&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982708%26dopt%3DAbstract Authors: Sellayah D, Bharaj P, Sikder D Abstract Orexin (OX) neuropeptides stimulate feeding and arousal. Deficiency of orexin is implicated in narcolepsy, a disease associated with obesity, paradoxically in the face of reduced food intake. Here, we show that obesity in orexin-null mice is associated with impaired brown adipose tissue (BAT) thermogenesis. Failure of thermogenesis in OX-null mice is due to inability of brown preadipocytes to differentiate. The differentiation defect in OX-null neonates is circumvented by OX injections to OX-null dams. In vitro, OX, triggers the full differentiation program in mesenchymal progenitor stem cells, embryonic fibroblasts and brown preadipocytes via p38 mitogen activated protein (MAP) kinase and bone morphogenetic protein receptor-1a (BMP... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313297 Wed, 05 Oct 2011 04:00:00 +0100 5313297 http://www.medworm.com/index.php?rid=5313296&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982709%26dopt%3DAbstract Authors: Lee KY, Gesta S, Boucher J, Wang XL, Kahn CR Abstract In obesity, adipocytes distant from vasculature become hypoxic and dysfunctional. This hypoxic response is mediated by hypoxia-inducible factors (Hif1α, Hif2α, and Hif3α) and their obligate partner, Hif1β (Arnt). We show that mice lacking Hif1β in fat (FH1βKO) are lean, exhibit reduced adipocyte size, and are protected from age- and diet-induced glucose intolerance. There is also reduced Vegf and vascular permeability in FH1βKO fat, but diet-induced inflammation and fibrosis is unchanged. Adipocytes from FH1βKO mice have reduced glucose uptake due to decreased Glut1 and Glut4, which is mirrored in 3T3-L1 adipocytes with Hif1β knockdown. Hif1β knockdown cells also fail to respond appropriately to hypoxia with r... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313296 Wed, 05 Oct 2011 04:00:00 +0100 5313296 http://www.medworm.com/index.php?rid=5313295&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982710%26dopt%3DAbstract Authors: Krahmer N, Guo Y, Wilfling F, Hilger M, Lingrell S, Heger K, Newman HW, Schmidt-Supprian M, Vance DE, Mann M, Farese RV, Walther TC Abstract Lipid droplets (LDs) are cellular storage organelles for neutral lipids that vary in size and abundance according to cellular needs. Physiological conditions that promote lipid storage rapidly and markedly increase LD volume and surface. How the need for surface phospholipids is sensed and balanced during this process is unknown. Here, we show that phosphatidylcholine (PC) acts as a surfactant to prevent LD coalescence, which otherwise yields large, lipolysis-resistant LDs and triglyceride (TG) accumulation. The need for additional PC to coat the enlarging surface during LD expansion is provided by the Kennedy pathway, which is activa... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313295 Wed, 05 Oct 2011 04:00:00 +0100 5313295 http://www.medworm.com/index.php?rid=5313294&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982711%26dopt%3DAbstract In this study, we utilize genetic loss of function experiments to show that constitutive activation of neither FoxA2 nor FoxO1 can account for the protection from steatosis afforded by deletion of Akt2 in liver. Rather, another downstream target positively regulated by Akt, the mTORC1 complex, is required in vivo for de novo lipogenesis and Srebp1c expression. Nonetheless, activation of mTORC1 and SREBP1c is not sufficient to drive postprandial lipogenesis in the absence of Akt2. These data show that insulin signaling through Akt2 promotes anabolic lipid metabolism independent of Foxa2 or FoxO1 and through pathways additional to the mTORC1-dependent activation of SREBP1c. PMID: 21982711 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313294 Wed, 05 Oct 2011 04:00:00 +0100 5313294 http://www.medworm.com/index.php?rid=5313293&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982712%26dopt%3DAbstract Authors: Yoshino J, Mills KF, Yoon MJ, Imai S Abstract Type 2 diabetes (T2D) has become epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, and the NAD(+)-dependent protein deacetylase SIRT1. Here, we show that NAMPT-mediated NAD(+) biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD(+) intermediate, ameliorates glucose intolerance by restoring NAD(+) levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313293 Wed, 05 Oct 2011 04:00:00 +0100 5313293 http://www.medworm.com/index.php?rid=5313292&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982713%26dopt%3DAbstract Authors: Tormos KV, Anso E, Hamanaka RB, Eisenbart J, Joseph J, Kalyanaraman B, Chandel NS Abstract Adipocyte differentiation is characterized by an increase in mitochondrial metabolism. However, it is not known whether the increase in mitochondrial metabolism is essential for differentiation or a byproduct of the differentiation process. Here, we report that primary human mesenchymal stem cells undergoing differentiation into adipocytes display an early increase in mitochondrial metabolism, biogenesis, and reactive oxygen species (ROS) generation. This early increase in mitochondrial metabolism and ROS generation was dependent on mTORC1 signaling. Mitochondrial-targeted antioxidants inhibited adipocyte differentiation, which was rescued by the addition of exogenous hydrogen peroxi... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313292 Wed, 05 Oct 2011 04:00:00 +0100 5313292 http://www.medworm.com/index.php?rid=5313291&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982714%26dopt%3DAbstract Authors: Hung YP, Albeck JG, Tantama M, Yellen G Abstract NADH is a key metabolic cofactor whose sensitive and specific detection in the cytosol of live cells has been difficult. We constructed a fluorescent biosensor of the cytosolic NADH-NAD(+) redox state by combining a circularly permuted GFP T-Sapphire with a bacterial NADH-binding protein, Rex. Although the initial construct reported [NADH] × [H(+)] / [NAD(+)], its pH sensitivity was eliminated by mutagenesis. The engineered biosensor Peredox reports cytosolic NADH:NAD(+) ratios and can be calibrated with exogenous lactate and pyruvate. We demonstrated its utility in several cultured and primary cell types. We found that glycolysis opposed the lactate dehydrogenase equilibrium to produce a reduced cytosolic NADH-NAD(+) redox... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313291 Wed, 05 Oct 2011 04:00:00 +0100 5313291 http://www.medworm.com/index.php?rid=5313290&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982715%26dopt%3DAbstract Authors: Zhao Y, Jin J, Hu Q, Zhou HM, Yi J, Yu Z, Xu L, Wang X, Yang Y, Loscalzo J Abstract We have developed genetically encoded fluorescent sensors for reduced nicotinamide adenine dinucleotide (NADH), which manifest a large change in fluorescence upon NADH binding. We demonstrate the utility of these sensors in mammalian cells by monitoring the dynamic changes in NADH levels in subcellular organelles as affected by NADH transport, glucose metabolism, electron transport chain function, and redox environment, and we demonstrate the temporal separation of changes in mitochondrial and cytosolic NADH levels with perturbation. These results support the view that cytosolic NADH is sensitive to environmental changes, while mitochondria have a strong tendency to maintain physiological N... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313290 Wed, 05 Oct 2011 04:00:00 +0100 5313290 http://www.medworm.com/index.php?rid=5313289&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982742%26dopt%3DAbstract Authors: Jimenez-Preitner M, Berney X, Uldry M, Vitali A, Cinti S, Ledford JG, Thorens B Abstract Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity. Brown adipogenesis requires activation of the transcription factor C/EBPβ and recruitment of the zinc finger protein Prdm16, but upstream inducers of these proteins are incompletely defined. Here, we show that genetic inactivation of Plac8, a gene encoding an evolutionarily conserved protein, induces cold intolerance, and late-onset obesity, as well as abnormal morphology and impaired function of brown adipocytes. Using brown preadipocyte lines we show that Plac8 is required for brown fat differentiation,... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313289 Mon, 03 Oct 2011 04:00:00 +0100 5313289 http://www.medworm.com/index.php?rid=5313288&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982743%26dopt%3DAbstract Authors: Patwari P, Emilsson V, Schadt EE, Chutkow WA, Lee S, Marsili A, Zhang Y, Dobrin R, Cohen DE, Larsen PR, Zavacki AM, Fong LG, Young SG, Lee RT Abstract A human genome-wide linkage scan for obesity identified a linkage peak on chromosome 5q13-15. Positional cloning revealed an association of a rare haplotype to high body-mass index (BMI) in males but not females. The risk locus contains a single gene, "arrestin domain-containing 3" (ARRDC3), an uncharacterized α-arrestin. Inactivating Arrdc3 in mice led to a striking resistance to obesity, with greater impact on male mice. Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues. AR... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5313288 Mon, 03 Oct 2011 04:00:00 +0100 5313288 http://www.medworm.com/index.php?rid=5219298&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907132%26dopt%3DAbstract Authors: Andrews NC Abstract Iron homeostasis is essential for life and health. In this issue of Cell Metabolism, Moroishi and colleagues (2011) show that FBXL5, an iron sensor in an ubiquitin ligase complex, keeps cellular iron in balance by promoting the degradation of IRP2 in vivo. PMID: 21907132 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219298 Wed, 07 Sep 2011 04:00:00 +0100 5219298 http://www.medworm.com/index.php?rid=5219297&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907133%26dopt%3DAbstract Authors: Tower J Abstract Human gut bacteria are implicated in normal metabolism as well as in diseases including diabetes and obesity. In this issue of Cell Metabolism,Storelli et al. (2011) report that a single Drosophila gut species, Lactobacillus plantarum, can promote larval growth by modulating TOR and hormonal growth signaling pathways, thereby providing an ideal duo for study of host-microbe interactions. PMID: 21907133 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219297 Wed, 07 Sep 2011 04:00:00 +0100 5219297 http://www.medworm.com/index.php?rid=5219296&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907134%26dopt%3DAbstract Authors: Deberardinis RJ Abstract Cancer cells display a reprogramming of metabolism that facilitates growth but addicts them to key enzyme activities. Two studies in Nature and Nature Genetics find that the gene encoding the serine biosynthetic enzyme phosphoglycerate dehydrogenase (PHGDH) is amplified in a subset of cancers and contributes to tumor cell growth. PMID: 21907134 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219296 Wed, 07 Sep 2011 04:00:00 +0100 5219296 http://www.medworm.com/index.php?rid=5219295&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907135%26dopt%3DAbstract Authors: Griffioen KJ, Mattson MP Abstract Laboratory animals usually become relatively insulin resistant and obese. In this issue of Cell Metabolism, Cao et al. (2011) find that mice living in a complex environment are resistant to diet-induced obesity because they produce energy-dissipating brown fat cells within white fat depots, a process orchestrated by brain-derived neurotrophic factor. PMID: 21907135 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219295 Wed, 07 Sep 2011 04:00:00 +0100 5219295 http://www.medworm.com/index.php?rid=5219294&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907136%26dopt%3DAbstract Authors: Barros RP, Gustafsson JÅ Abstract The metabolic syndrome has reached pandemic level worldwide, and evidence is that estradiol plays a key role in its development. The discovery of the second estrogen receptor, ERβ, in tissues previously not considered targets of estradiol was a breakthrough in endocrinology. In the present review, we discuss how the presence of ERβ and the previously described ERα in tissues involved in glucose and lipid homeostasis (brain, skeletal muscle, adipose tissue, pancreas, liver, and heart) may have important implications to risk factors associated with the metabolic syndrome. Imbalance of ERα/ERβ ratio in this "metabolic network" may lead to the metabolic syndrome. PMID: 21907136 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219294 Wed, 07 Sep 2011 04:00:00 +0100 5219294 http://www.medworm.com/index.php?rid=5219293&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907137%26dopt%3DAbstract Authors: Ramadori G, Fujikawa T, Anderson J, Berglund ED, Frazao R, Michán S, Vianna CR, Sinclair DA, Elias CF, Coppari R Abstract Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219293 Wed, 07 Sep 2011 04:00:00 +0100 5219293 http://www.medworm.com/index.php?rid=5219292&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907138%26dopt%3DAbstract Authors: Leinninger GM, Opland DM, Jo YH, Faouzi M, Christensen L, Cappellucci LA, Rhodes CJ, Gnegy ME, Becker JB, Pothos EN, Seasholtz AF, Thompson RC, Myers MG Abstract Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb(Nts) neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219292 Wed, 07 Sep 2011 04:00:00 +0100 5219292 http://www.medworm.com/index.php?rid=5219291&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907139%26dopt%3DAbstract Authors: Cao L, Choi EY, Liu X, Martin A, Wang C, Xu X, During MJ Abstract Living in an enriched environment with complex physical and social stimulation leads to improved cognitive and metabolic health. In white fat, enrichment induced the upregulation of the brown fat cell fate determining gene Prdm16, brown fat-specific markers, and genes involved in thermogenesis and β-adrenergic signaling. Moreover, pockets of cells with prototypical brown fat morphology and high UCP1 levels were observed in the white fat of enriched mice associated with resistance to diet-induced obesity. Hypothalamic overexpression of BDNF reproduced the enrichment-associated activation of the brown fat gene program and lean phenotype. Inhibition of BDNF signaling by genetic knockout or dominant-negative tr... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219291 Wed, 07 Sep 2011 04:00:00 +0100 5219291 http://www.medworm.com/index.php?rid=5219290&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907140%26dopt%3DAbstract Authors: Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI Abstract Iron-dependent degradation of iron-regulatory protein 2 (IRP2) is a key event for maintenance of an appropriate intracellular concentration of iron. Although FBXL5 (F box and leucine-rich repeat protein 5) is thought to mediate this degradation, the role of FBXL5 in the control of iron homeostasis in vivo has been poorly understood. We have now found that mice deficient in FBXL5 died in utero, associated with excessive iron accumulation. This embryonic mortality was prevented by additional ablation of IRP2, suggesting that impaired IRP2 degradation is primarily responsible for the death of Fbxl5(-)(/-) mice. We also found that liver-specific deletion of Fbxl5 resulted in deregulation of both hepatic and syste... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219290 Wed, 07 Sep 2011 04:00:00 +0100 5219290 http://www.medworm.com/index.php?rid=5219289&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907141%26dopt%3DAbstract Authors: McCormick JA, Mutig K, Nelson JH, Saritas T, Hoorn EJ, Yang CL, Rogers S, Curry J, Delpire E, Bachmann S, Ellison DH Abstract The renal thick ascending limb (TAL) and distal convoluted tubule (DCT) play central roles in salt homeostasis and blood pressure regulation. An emerging model suggests that bumetanide- and thiazide-sensitive NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1. Here, we show that a kidney-specific SPAK isoform, which lacks the kinase domain, inhibits phosphorylation of NCC and NKCC2 by full-length SPAK in vitro. Kidney-specific SPAK is highly expressed along the TAL, whereas full-length SPAK is more highly expressed along the DCT. As predicted from the differential expression, SP... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219289 Wed, 07 Sep 2011 04:00:00 +0100 5219289 http://www.medworm.com/index.php?rid=5219288&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907142%26dopt%3DAbstract Authors: Esterházy D, Stützer I, Wang H, Rechsteiner MP, Beauchamp J, Döbeli H, Hilpert H, Matile H, Prummer M, Schmidt A, Lieske N, Boehm B, Marselli L, Bosco D, Kerr-Conte J, Aebersold R, Spinas GA, Moch H, Migliorini C, Stoffel M Abstract Decreased β cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human β cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented β cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219288 Wed, 07 Sep 2011 04:00:00 +0100 5219288 http://www.medworm.com/index.php?rid=5219287&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907143%26dopt%3DAbstract Authors: Xie X, Gong Z, Mansuy-Aubert V, Zhou QL, Tatulian SA, Sehrt D, Gnad F, Brill LM, Motamedchaboki K, Chen Y, Czech MP, Mann M, Krüger M, Jiang ZY Abstract The protein kinase B(β) (Akt2) pathway is known to mediate insulin-stimulated glucose transport through increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane (PM). Combining quantitative phosphoproteomics with RNAi-based functional analyses, we show that a previously uncharacterized 138 kDa C2 domain-containing phosphoprotein (CDP138) is a substrate for Akt2, and is required for optimal insulin-stimulated glucose transport, GLUT4 translocation, and fusion of GLUT4 vesicles with the PM in live adipocytes. The purified C2 domain is capable of binding Ca(2+) and lipid membrane... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219287 Wed, 07 Sep 2011 04:00:00 +0100 5219287 http://www.medworm.com/index.php?rid=5219286&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907144%26dopt%3DAbstract Authors: Tan KT, Luo SC, Ho WZ, Lee YH Abstract Upon nutrient deprivation, cells are thought to suppress biosynthesis but activate catabolic pathways to provide alternative energy sources and nutrients. However, here we provide evidence that in adult male C. elegans, both biosynthesis and degradation activities, including ribosome biogenesis and turnover, are enhanced during early starvation and appear to depend on the availability of intestinal lipid stores. Upon depletion of the intestinal lipids, further food deprivation results in a significant reduction in metabolic activity in the starved male worms. Our data show that adult C. elegans exhibits a two-phase metabolic response to starvation stress: an initial phase with enhanced metabolic activity that rapidly exhausts the li... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219286 Wed, 07 Sep 2011 04:00:00 +0100 5219286 http://www.medworm.com/index.php?rid=5219285&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907145%26dopt%3DAbstract Authors: Storelli G, Defaye A, Erkosar B, Hols P, Royet J, Leulier F Abstract There is growing evidence that intestinal bacteria are important beneficial partners of their metazoan hosts. Recent observations suggest a strong link between commensal bacteria, host energy metabolism, and metabolic diseases such as diabetes and obesity. As a consequence, the gut microbiota is now considered a "host" factor that influences energy uptake. However, the impact of intestinal bacteria on other systemic physiological parameters still remains unclear. Here, we demonstrate that Drosophila microbiota promotes larval growth upon nutrient scarcity. We reveal that Lactobacillus plantarum, a commensal bacterium of the Drosophila intestine, is sufficient on its own to recapitulate the natural microb... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219285 Wed, 07 Sep 2011 04:00:00 +0100 5219285 http://www.medworm.com/index.php?rid=5219284&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907146%26dopt%3DAbstract Authors: Grüning NM, Rinnerthaler M, Bluemlein K, Mülleder M, Wamelink MM, Lehrach H, Jakobs C, Breitenbach M, Ralser M Abstract In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism when respiration is activated. Low PYK activity activated yeast respiration. However, levels of reactive oxygen species (ROS) did not increase, and cells gained resistance to oxidants. This adaptation was attributable to accumulation of the PYK substrate phosphoenolpyruvate (PEP). PEP acted as feedback inhibitor of the glycolytic enzyme triosephosphate isome... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219284 Wed, 07 Sep 2011 04:00:00 +0100 5219284 http://www.medworm.com/index.php?rid=5219283&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907147%26dopt%3DAbstract Authors: Tucker EJ, Hershman SG, Köhrer C, Belcher-Timme CA, Patel J, Goldberger OA, Christodoulou J, Silberstein JM, McKenzie M, Ryan MT, Compton AG, Jaffe JD, Carr SA, Calvo SE, Rajbhandary UL, Thorburn DR, Mootha VK Abstract The metazoan mitochondrial translation machinery is unusual in having a single tRNA(Met) that fulfills the dual role of the initiator and elongator tRNA(Met). A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation; however, the requirement of formylation for initiation in human mitochondria is still under debate. Using targeted sequencing of the mtDNA and nuclear exons encoding the mitochondrial proteome (M... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5219283 Wed, 07 Sep 2011 04:00:00 +0100 5219283 http://www.medworm.com/index.php?rid=5104197&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803281%26dopt%3DAbstract Authors: Panopoulos AD, Izpisua Belmonte JC Reprogramming involves multiple layers of molecular regulation, yet it remains relatively unknown how the cell's metabolism is changing and/or contributing to this process. In this issue of Cell Metabolism, Folmes et al. (2011) demonstrate that reprogramming induces a bioenergetic transition from an oxidative to a glycolytic state, and provide evidence to suggest that these changes may precede pluripotency. PMID: 21803281 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104197 Tue, 02 Aug 2011 23:00:00 +0100 5104197 http://www.medworm.com/index.php?rid=5104196&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803282%26dopt%3DAbstract Authors: Rubinstein M, Low MJ Hypothalamic pro-opiomelanocortin (POMC) neurons are the major source of anorectic melanocortin peptides in the brain. A recent study (Mineur et al., 2011) demonstrates that nicotine directly stimulates arcuate POMC neurons through nicotinic acetylcholinergic α3β4 receptors, suggesting a new mechanism to understand the inverse relationship between tobacco smoking and body weight. PMID: 21803282 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104196 Tue, 02 Aug 2011 23:00:00 +0100 5104196 http://www.medworm.com/index.php?rid=5104195&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803283%26dopt%3DAbstract Authors: Lunyak VV, Kennedy BK Defining the molecular events that precipitate multisystem decline is an important component of aging research. In this issue, Jin et al. (2011) show that increased expression of the histone demethylase, utx-1, causes genome-wide decreases in histone H3K27 trimethylation, which includes the insulin/IGF-1 signaling (IIS) pathway that promotes aging. PMID: 21803283 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104195 Tue, 02 Aug 2011 23:00:00 +0100 5104195 http://www.medworm.com/index.php?rid=5104194&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803284%26dopt%3DAbstract Authors: Näär AM MicroRNAs (miRNAs) have recently been found to be critical regulators of metabolic homeostasis. A study in Nature by Trajkovski et al. (2011) shows that the highly related miRNAs miR-103 and miR-107 modulate insulin sensitivity and glucose homeostasis in obese mice. These miRNAs might represent therapeutic targets to ameliorate obesity-associated insulin resistance. PMID: 21803284 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104194 Tue, 02 Aug 2011 23:00:00 +0100 5104194 http://www.medworm.com/index.php?rid=5104193&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803285%26dopt%3DAbstract Authors: Guarente L Protein acetylation now rivals phosphorylation in frequency of occurrence but is incompletely understood. A picture is presented in which protein acetylation is linked to available energy via the NAD-dependent deacetylases. This model suggests that protein acetylation regulates metabolic strategy and also helps store energy in cells. PMID: 21803285 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104193 Tue, 02 Aug 2011 23:00:00 +0100 5104193 http://www.medworm.com/index.php?rid=5104192&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803286%26dopt%3DAbstract Authors: Piper MD, Partridge L, Raubenheimer D, Simpson SJ Dietary restriction (DR) and mutations in nutrient signaling pathways can extend healthy life span in diverse organisms. Studying the interaction between these interventions should reveal mechanisms of aging, but has yielded some apparently contradictory results. A multidimensional representation of nutrition, called the geometric framework, can better describe the responses of life span and other traits, including metabolism, and can reconcile these apparent contradictions. We provide examples showing that it is more informative to analyze DR in terms of dietary balance and that dietary optimization for life span is critical for studies examining the biology of aging and other traits. PMID: 21803286 [PubMed - in process] (... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104192 Tue, 02 Aug 2011 23:00:00 +0100 5104192 http://www.medworm.com/index.php?rid=5104191&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803287%26dopt%3DAbstract Authors: Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, Huang X, Cao X, Yan Z, Hou L, Liu J, Shukeir N, Khaitovich P, Chen CD, Zhang H, Jenuwein T, Han JD Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104191 Tue, 02 Aug 2011 23:00:00 +0100 5104191 http://www.medworm.com/index.php?rid=5104190&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803288%26dopt%3DAbstract Authors: Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM, Singh R Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the failure to upregulate AgRP in response to starvation, and constitutive increases in hypothalamic levels of pro-opiomelanocortin and its cleavage product α-melanocyte-stimulating hormone that typic... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104190 Tue, 02 Aug 2011 23:00:00 +0100 5104190 http://www.medworm.com/index.php?rid=5104189&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803289%26dopt%3DAbstract Authors: Birkenfeld AL, Lee HY, Guebre-Egziabher F, Alves TC, Jurczak MJ, Jornayvaz FR, Zhang D, Hsiao JJ, Martin-Montalvo A, Fischer-Rosinsky A, Spranger J, Pfeiffer AF, Jordan J, Fromm MF, König J, Lieske S, Carmean CM, Frederick DW, Weismann D, Knauf F, Irusta PM, De Cabo R, Helfand SL, Samuel VT, Shulman GI Reduced expression of the Indy (I'm Not Dead, Yet) gene in D. melanogaster and its homolog in C. elegans prolongs life span and in D. melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mIndy in mice (mINDY(-/-) mice) reduces hepatocellular ATP/ADP ratio, activates hepat... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104189 Tue, 02 Aug 2011 23:00:00 +0100 5104189 http://www.medworm.com/index.php?rid=5104188&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803290%26dopt%3DAbstract Authors: Andersson DC, Betzenhauser MJ, Reiken S, Meli AC, Umanskaya A, Xie W, Shiomi T, Zalk R, Lacampagne A, Marks AR Age-related loss of muscle mass and force (sarcopenia) contributes to disability and increased mortality. Ryanodine receptor 1 (RyR1) is the skeletal muscle sarcoplasmic reticulum calcium release channel required for muscle contraction. RyR1 from aged (24 months) rodents was oxidized, cysteine-nitrosylated, and depleted of the channel-stabilizing subunit calstabin1, compared to RyR1 from younger (3-6 months) adults. This RyR1 channel complex remodeling resulted in "leaky" channels with increased open probability, leading to intracellular calcium leak in skeletal muscle. Similarly, 6-month-old mice harboring leaky RyR1-S2844D mutant channels exhibited skeletal muscle... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104188 Tue, 02 Aug 2011 23:00:00 +0100 5104188 http://www.medworm.com/index.php?rid=5104187&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803291%26dopt%3DAbstract Authors: Pihlajamäki J, Lerin C, Itkonen P, Boes T, Floss T, Schroeder J, Dearie F, Crunkhorn S, Burak F, Jimenez-Chillaron JC, Kuulasmaa T, Miettinen P, Park PJ, Nasser I, Zhao Z, Zhang Z, Xu Y, Wurst W, Ren H, Morris AJ, Stamm S, Goldfine AB, Laakso M, Patti ME Alternative mRNA splicing provides transcript diversity and may contribute to human disease. We demonstrate that expression of several genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. We evaluated a representative splicing factor, SFRS10, downregulated in both obese human liver and muscle and in high-fat-fed mice, and determined metabolic impact of reduced expression. SFRS10-specific siRNA induces lipogenesis and lipid accumulation in hepatocytes. Moreover, Sfrs10 heterozygous mi... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104187 Tue, 02 Aug 2011 23:00:00 +0100 5104187 http://www.medworm.com/index.php?rid=5104186&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803292%26dopt%3DAbstract Authors: Bedford DC, Kasper LH, Wang R, Chang Y, Green DR, Brindle PK Opposing activities of acetyltransferases and deacetylases help regulate energy balance. Mice heterozygous for the acetyltransferase CREB binding protein (CBP) are lean and insulin sensitized, but how CBP regulates energy homeostasis is unclear. In one model, the main CBP interaction with the glucagon-responsive factor CREB is not limiting for liver gluconeogenesis, whereas a second model posits that Ser436 in the CH1 (TAZ1) domain of CBP is required for insulin and the antidiabetic drug metformin to inhibit CREB-mediated liver gluconeogenesis. Here we show that conditional knockout of CBP in liver does not decrease fasting blood glucose or gluconeogenic gene expression, consistent with the first model. However, mice... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104186 Tue, 02 Aug 2011 23:00:00 +0100 5104186 http://www.medworm.com/index.php?rid=5104185&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803293%26dopt%3DAbstract Authors: Yamazaki D, Tabara Y, Kita S, Hanada H, Komazaki S, Naitou D, Mishima A, Nishi M, Yamamura H, Yamamoto S, Kakizawa S, Miyachi H, Yamamoto S, Miyata T, Kawano Y, Kamide K, Ogihara T, Hata A, Umemura S, Soma M, Takahashi N, Imaizumi Y, Miki T, Iwamoto T, Takeshima H TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104185 Tue, 02 Aug 2011 23:00:00 +0100 5104185 http://www.medworm.com/index.php?rid=5104184&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803294%26dopt%3DAbstract Authors: Moreno-Aliaga MJ, Pérez-Echarri N, Marcos-Gómez B, Larequi E, Gil-Bea FJ, Viollet B, Gimenez I, Martínez JA, Prieto J, Bustos M Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. We observed that ct-1(-/-) mice develop mature-onset obesity, insulin resistance, and hypercholesterolemia despite reduced calorie intake. Decreased energy expenditure preceded and accompanied the development of obesity. Acute treatment with rCT-1 decreased blood glucose in an insulin-independent manner and increased insulin-stimulated AKT phosphorylation in muscle. These changes were associated with stimulation of fatty acid oxidation, an effect that was absent in AMPKα2(-/-) mice. Chronic rCT-1 treatment reduced food intake, enhanced energy expenditure, and induced white adipo... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104184 Tue, 02 Aug 2011 23:00:00 +0100 5104184 http://www.medworm.com/index.php?rid=5104183&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803295%26dopt%3DAbstract Authors: Khodthong C, Kabachinski G, James DJ, Martin TF Neuropeptide and peptide hormone secretion from neural and endocrine cells occurs by Ca(2+)-triggered dense-core vesicle exocytosis. The membrane fusion machinery consisting of vesicle and plasma membrane SNARE proteins needs to be assembled for Ca(2+)-triggered vesicle exocytosis. The related Munc13 and CAPS/UNC31 proteins that prime vesicle exocytosis are proposed to promote SNARE complex assembly. CAPS binds SNARE proteins and stimulates SNARE complex formation on liposomes, but the relevance of SNARE binding to CAPS function in cells had not been determined. Here we identify a core SNARE-binding domain in CAPS as corresponding to Munc13 homology domain-1 (MHD1). CAPS lacking a single helix in MHD1 was unable to bind SNARE pro... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104183 Tue, 02 Aug 2011 23:00:00 +0100 5104183 http://www.medworm.com/index.php?rid=5104182&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803296%26dopt%3DAbstract Authors: Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C, Terzic A The bioenergetics of somatic dedifferentiation into induced pluripotent stem cells remains largely unknown. Here, stemness factor-mediated nuclear reprogramming reverted mitochondrial networks into cristae-poor structures. Metabolomic footprinting and fingerprinting distinguished derived pluripotent progeny from parental fibroblasts according to elevated glucose utilization and production of glycolytic end products. Temporal sampling demonstrated glycolytic gene potentiation prior to induction of pluripotent markers. Functional metamorphosis of  somatic oxidative phosphorylation into acquired pluripotent glycolytic metabolism conformed to an embryonic-like archetype.... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104182 Tue, 02 Aug 2011 23:00:00 +0100 5104182 http://www.medworm.com/index.php?rid=5104181&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803297%26dopt%3DAbstract In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner. PMID: 21803297 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5104181 Tue, 02 Aug 2011 23:00:00 +0100 5104181 http://www.medworm.com/index.php?rid=5009196&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723496%26dopt%3DAbstract Authors: Mattijssen F, Kersten S Lipotoxicity describes the process of cellular dysfunction in response to lipid overload. In this issue of Cell Metabolism, Michel and colleagues (2011) provide evidence for a role of snoRNAs in palmitate-induced oxidative stress. PMID: 21723496 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009196 Tue, 05 Jul 2011 23:00:00 +0100 5009196 http://www.medworm.com/index.php?rid=5009195&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723497%26dopt%3DAbstract Authors: Rahmouni K, Davisson RL, Sigmund CD Obesity and hypertension are strongly associated, and neural dysfunction has been implicated in both. The hypothalamus integrates signals regulating blood pressure and energy homeostasis. A recent paper in Nature Medicine (Purkayastha et al., 2011) suggests that obesity and hypertension are caused by inflammation in distinct hypothalamic neuronal populations. PMID: 21723497 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009195 Tue, 05 Jul 2011 23:00:00 +0100 5009195 http://www.medworm.com/index.php?rid=5009194&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723498%26dopt%3DAbstract Authors: Taborsky GJ The autonomic nervous system influences insulin and glucagon secretion. In this issue, Rodriguez-Diaz et al. (2011) show that mouse and human islets differ in their innervation patterns, yet the effect of neural activation on islet hormone secretion is similar. Key questions raised by this species difference have potential relevance to diabetic therapeutics. PMID: 21723498 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009194 Tue, 05 Jul 2011 23:00:00 +0100 5009194 http://www.medworm.com/index.php?rid=5009193&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723499%26dopt%3DAbstract Authors: Mehta NN, Rader DJ The field of vascular molecular imaging is searching for the "holy grail" of an imaging technique that will quantitatively and reliably assess vulnerable coronary plaques. Fluorescence imaging with indocyanine green specifically identifies lipid-rich plaques in rabbits and in humans and represents a promising, though invasive, approach. PMID: 21723499 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009193 Tue, 05 Jul 2011 23:00:00 +0100 5009193 http://www.medworm.com/index.php?rid=5009192&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723500%26dopt%3DAbstract Authors: Lin HV, Accili D We review mechanisms that regulate production of glucose by the liver, focusing on areas of budding consensus, and endeavoring to provide a candid assessment of lingering controversies. We also attempt to reconcile data from tracer studies in humans and large animals with the growing compilation of mouse knockouts that display changes in glucose production. A clinical hallmark of diabetes, excessive glucose production remains key to its treatment. Hence, we attempt to integrate emerging pathways into the broader goal to rejuvenate the staid antidiabetic pharmacopeia. PMID: 21723500 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009192 Tue, 05 Jul 2011 23:00:00 +0100 5009192 http://www.medworm.com/index.php?rid=5009191&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723501%26dopt%3DAbstract Authors: Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, Lipovsky AI, Gorgun C, Kwiatkowski DJ, Hotamisligil GS, Lee CH, Manning BD Through unknown mechanisms, insulin activates the sterol regulatory element-binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We find that this induction is dependent on the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). To further define the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 (LTsc1KO), which results in insulin-independent activation of mTORC1. Surprisingly, the LTsc1KO mice are protected from age- and diet-induced hepatic steatosis and display hepatocyte-intrinsic defects in SREBP1c activation and de novo lipogenesis. These phenotypes resul... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009191 Tue, 05 Jul 2011 23:00:00 +0100 5009191 http://www.medworm.com/index.php?rid=5009190&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723502%26dopt%3DAbstract Authors: Michel CI, Holley CL, Scruggs BS, Sidhu R, Brookheart RT, Listenberger LL, Behlke MA, Ory DS, Schaffer JE Lipotoxicity is a metabolic stress response implicated in the pathogenesis of diabetes complications and has been shown to involve lipid-induced oxidative stress. To elucidate the molecular mechanisms of lipotoxicity, we used retroviral promoter trap mutagenesis to isolate a cell line that is resistant to lipotoxic and oxidative stress. We show that loss of three box C/D small nucleolar RNAs (snoRNAs) encoded in the ribosomal protein L13a (rpL13a) locus is sufficient to confer resistance to lipotoxic and oxidative stress in vitro and prevents the propagation of oxidative stress in vivo. Our results provide evidence for a previously unappreciated, non-canonical role for b... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009190 Tue, 05 Jul 2011 23:00:00 +0100 5009190 http://www.medworm.com/index.php?rid=5009189&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723503%26dopt%3DAbstract Authors: Rodriguez-Diaz R, Abdulreda MH, Formoso AL, Gans I, Ricordi C, Berggren PO, Caicedo A The autonomic nervous system regulates hormone secretion from the endocrine pancreas, the islets of Langerhans, thus impacting glucose metabolism. The parasympathetic and sympathetic nerves innervate the pancreatic islet, but the precise innervation patterns are unknown, particularly in human. Here we demonstrate that the innervation of human islets is different from that of mouse islets and does not conform to existing models of autonomic control of islet function. By visualizing axons in three dimensions and quantifying axonal densities and contacts within pancreatic islets, we found that, unlike mouse endocrine cells, human endocrine cells are sparsely contacted by autonomic axons. Few par... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009189 Tue, 05 Jul 2011 23:00:00 +0100 5009189 http://www.medworm.com/index.php?rid=5009188&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723504%26dopt%3DAbstract Authors: Rogers AN, Chen D, McColl G, Czerwieniec G, Felkey K, Gibson BW, Hubbard A, Melov S, Lithgow GJ, Kapahi P Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon I... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009188 Tue, 05 Jul 2011 23:00:00 +0100 5009188 http://www.medworm.com/index.php?rid=5009187&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723505%26dopt%3DAbstract Authors: Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, Zerfas P, Zhigang D, Wright EC, Stuelten C, Sun P, Lonning S, Skarulis M, Sumner AE, Finkel T, Rane SG Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-β/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3-deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3(-)(/-) white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3(-/-) adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, an... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009187 Tue, 05 Jul 2011 23:00:00 +0100 5009187 http://www.medworm.com/index.php?rid=5009186&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723506%26dopt%3DAbstract Authors: Viscomi C, Bottani E, Civiletto G, Cerutti R, Moggio M, Fagiolari G, Schon EA, Lamperti C, Zeviani M Increased mitochondrial biogenesis by activation of PPAR- or AMPK/PGC-1α-dependent homeostatic pathways has been proposed as a treatment for mitochondrial disease. We tested this hypothesis on three recombinant mouse models characterized by defective cytochrome c-oxidase (COX) activity: a knockout (KO) mouse for Surf1, a knockout/knockin mouse for Sco2, and a muscle-restricted KO mouse for Cox15. First, we demonstrated that double-recombinant animals overexpressing PGC-1α in skeletal muscle on a Surf1 KO background showed robust induction of mitochondrial biogenesis and increase of mitochondrial respiratory chain activities, including COX. No such effect was obtained by trea... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009186 Tue, 05 Jul 2011 23:00:00 +0100 5009186 http://www.medworm.com/index.php?rid=5009185&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723507%26dopt%3DAbstract Authors: Jin X, Moskophidis D, Mivechi NF Hepatocellular carcinoma (HCC) occurrence and progression are linked tightly to progressive hepatic metabolic syndrome associated with insulin resistance, hepatic steatosis, and chronic inflammation. Heat shock transcription factor 1 (HSF1), a major transactivator of stress proteins, increases survival by protecting cells against environmental stressors. It has been implicated in the pathogenesis of cancer, but specific mechanisms by which HSF1 supports cancer development remain elusive. We propose a pathogenic mechanism whereby HSF1 activation promotes growth of premalignant cells and HCC development by stimulating lipid biosynthesis and perpetuating chronic hepatic metabolic disease induced by carcinogens. Our work shows that inactivation of ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009185 Tue, 05 Jul 2011 23:00:00 +0100 5009185 http://www.medworm.com/index.php?rid=5009184&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723508%26dopt%3DAbstract Authors: Wong WT, Tian XY, Xu A, Yu J, Lau CW, Hoo RL, Wang Y, Lee VW, Lam KS, Vanhoutte PM, Huang Y Rosiglitazone is a PPARγ agonist commonly used to treat diabetes. In addition to improving insulin sensitivity, rosiglitazone restores normal vascular function by a mechanism that remains poorly understood. Here we show that adiponectin is required to mediate the PPARγ effect on vascular endothelium of diabetic mice. In db/db and diet-induced obese mice, PPARγ activation by rosiglitazone restores endothelium-dependent relaxation of aortae, whereas diabetic mice lacking adiponectin or treated with an anti-adiponectin antibody do not respond. Rosiglitazone stimulates adiponectin release from fat explants, and subcutaneous fat transplantation from rosiglitazone-treated mice recapitulate... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009184 Tue, 05 Jul 2011 23:00:00 +0100 5009184 http://www.medworm.com/index.php?rid=5009183&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723509%26dopt%3DAbstract Authors: Tang W, Zeve D, Seo J, Jo AY, Graff JM White adipose tissue regulates metabolism; the importance of this control is highlighted by the ongoing pandemic of obesity and associated complications such as diabetes, atherosclerosis, and cancer. White adipose tissue maintenance is a dynamic process, yet very little is known about how pharmacologic stimuli affect such plasticity. Combining in vivo lineage marking and BrdU labeling strategies, we found that rosiglitazone, a member of the thiazolidinedione class of glucose-lowering medicines, markedly increases the evolution of adipose progenitors into adipocytes. Notably, chronic rosiglitazone administration disrupts the adipogenic and self-renewal capacities of the stem cell compartment and alters its molecular characteristics. Thes... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009183 Tue, 05 Jul 2011 23:00:00 +0100 5009183 http://www.medworm.com/index.php?rid=5009182&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723510%26dopt%3DAbstract Authors: Rose AJ, Díaz MB, Reimann A, Klement J, Walcher T, Krones-Herzig A, Strobel O, Werner J, Peters A, Kleyman A, Tuckermann JP, Vegiopoulos A, Herzig S Systemic bile acid (BA) homeostasis is a critical determinant of dietary fat digestion, enterohepatic function, and postprandial thermogenesis. However, major checkpoints for the dynamics and the molecular regulation of BA homeostasis remain unknown. Here we show that hypothalamic-pituitary-adrenal (HPA) axis impairment in humans and liver-specific deficiency of the glucocorticoid receptor (GR) in mice disrupts the normal changes in systemic BA distribution during the fasted-to-fed transition. Fasted mice with hepatocyte-specific GR knockdown had smaller gallbladder BA content and were more susceptible to developing cholesterol g... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009182 Tue, 05 Jul 2011 23:00:00 +0100 5009182 http://www.medworm.com/index.php?rid=5009181&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723511%26dopt%3DAbstract Authors: Hu S, Balakrishnan A, Bok RA, Anderton B, Larson PE, Nelson SJ, Kurhanewicz J, Vigneron DB, Goga A Tumor cells have an altered metabolic phenotype characterized by increased glycolysis and diminished oxidative phosphorylation. Despite the suspected importance of glycolysis in tumorigenesis, the temporal relationship between oncogene signaling, in vivo tumor formation, and glycolytic pathway activity is poorly understood. Moreover, how glycolytic pathways are altered as tumors regress remains unknown. Here, we use a switchable model of Myc-driven liver cancer, along with hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) to visualize glycolysis in de novo tumor formation and regression. LDHA abundance and activity in tumors is tightly correlated to ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=5009181 Tue, 05 Jul 2011 23:00:00 +0100 5009181 http://www.medworm.com/index.php?rid=4962293&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641540%26dopt%3DAbstract Authors: Gill S, Panda S The diurnally active fruit flies prefer a major meal in the morning. Feeding the flies in the evening uncouples their metabolic cycle from circadian activity rhythms. A paper by Xu et al. in this issue of Cell Metabolism found that such uncoupled rhythms reduce egg laying. PMID: 21641540 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962293 Tue, 07 Jun 2011 23:00:00 +0100 4962293 http://www.medworm.com/index.php?rid=4962292&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641541%26dopt%3DAbstract Authors: El-Kouhen K, Tremblay ML Cardiolipin, a phospholipid component of the inner mitochondrial membrane, is required for mitochondrial metabolism. In this issue, Zhang et al. (2011) highlight a critical role for PTPMT1, a mitochondrial phosphatase, in cardiolipin biogenesis and possibly in cardiolipin deficiency diseases. Their findings also unveil a yet uncharacterized pathway affecting cell growth. PMID: 21641541 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962292 Tue, 07 Jun 2011 23:00:00 +0100 4962292 http://www.medworm.com/index.php?rid=4962291&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641542%26dopt%3DAbstract Authors: Lamming DW, Sabatini DM TOR (target of rapamycin) signaling regulates life span in many organisms, but the mechanism behind the effect is unknown. In this issue of Cell Metabolism, Pan and colleagues (2011) find that reduced TORC1 activity promotes yeast life span via a mechanism that, paradoxically, relies upon the production of normally deleterious reactive oxygen species. PMID: 21641542 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962291 Tue, 07 Jun 2011 23:00:00 +0100 4962291 http://www.medworm.com/index.php?rid=4962290&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641543%26dopt%3DAbstract Authors: Ellison DH, Brooks VL Roles of the sympathetic nervous system versus kidney salt transporters in hypertension are debated. A study in Nature Medicine (Mu et al., 2011) shows that dietary salt excess, coupled with β-adrenergic stimulation, increases arterial pressure via glucocorticoid receptors and WNK4, suggesting interactions between these systems in the pathogenesis of hypertension. PMID: 21641543 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962290 Tue, 07 Jun 2011 23:00:00 +0100 4962290 http://www.medworm.com/index.php?rid=4962289&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641544%26dopt%3DAbstract Authors: Zhong L, Mostoslavsky R Sirtuins have emerged in recent years as critical regulators of metabolism, influencing numerous facets of energy and nutrient homeostasis. Here, we review recent advances on the role of this fascinating family of mammalian proteins and their well-orchestrated function in modulating mitochondrial activity. PMID: 21641544 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962289 Tue, 07 Jun 2011 23:00:00 +0100 4962289 http://www.medworm.com/index.php?rid=4962288&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641545%26dopt%3DAbstract Authors: Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962288 Tue, 07 Jun 2011 23:00:00 +0100 4962288 http://www.medworm.com/index.php?rid=4962287&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641546%26dopt%3DAbstract Authors: Xu K, Diangelo JR, Hughes ME, Hogenesch JB, Sehgal A Circadian rhythms are regulated by a synchronized system of central and peripheral clocks. Here, we show that a clock in the Drosophila fat body drives rhythmic expression of genes involved in metabolism, detoxification, the immune response, and steroid hormone regulation. Some of these genes cycle even when the fat body clock is disrupted, indicating that they are regulated by exogenous factors. Food is an important stimulus, as limiting food availability to a 6 hr interval each day drives rhythmic expression of genes in the fat body. Restricting food to a time of day when consumption is typically low desynchronizes internal rhythms because it alters the phase of rhythmic gene expression in the fat body without affecting t... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962287 Tue, 07 Jun 2011 23:00:00 +0100 4962287 http://www.medworm.com/index.php?rid=4962286&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641547%26dopt%3DAbstract Authors: Ouimet M, Franklin V, Mak E, Liao X, Tabas I, Marcel YL The lipid droplet (LD) is the major site of cholesterol storage in macrophage foam cells and is a potential therapeutic target for the treatment of atherosclerosis. Cholesterol, stored as cholesteryl esters (CEs), is liberated from this organelle and delivered to cholesterol acceptors. The current paradigm attributes all cytoplasmic CE hydrolysis to the action of neutral CE hydrolases. Here, we demonstrate an important role for lysosomes in LD CE hydrolysis in cholesterol-loaded macrophages, in addition to that mediated by neutral hydrolases. Furthermore, we demonstrate that LDs are delivered to lysosomes via autophagy, where lysosomal acid lipase (LAL) acts to hydrolyze LD CE to generate free cholesterol mainly for ABCA1... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962286 Tue, 07 Jun 2011 23:00:00 +0100 4962286 http://www.medworm.com/index.php?rid=4962285&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641548%26dopt%3DAbstract Authors: Pan Y, Schroeder EA, Ocampo A, Barrientos A, Shadel GS Here we show that yeast strains with reduced target of rapamycin (TOR) signaling have greater overall mitochondrial electron transport chain activity during growth that is efficiently coupled to ATP production. This metabolic alteration increases mitochondrial membrane potential and reactive oxygen species (ROS) production, which we propose supplies an adaptive signal during growth that extends chronological life span (CLS). In strong support of this concept, uncoupling respiration during growth or increasing expression of mitochondrial manganese superoxide dismutase significantly curtails CLS extension in tor1Δ strains, and treatment of wild-type strains with either rapamycin (to inhibit TORC1) or menadione (to generate ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962285 Tue, 07 Jun 2011 23:00:00 +0100 4962285 http://www.medworm.com/index.php?rid=4962284&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641549%26dopt%3DAbstract Authors: Deyev IE, Sohet F, Vassilenko KP, Serova OV, Popova NV, Zozulya SA, Burova EB, Houillier P, Rzhevsky DI, Berchatova AA, Murashev AN, Chugunov AO, Efremov RG, Nikol'sky NN, Bertelli E, Eladari D, Petrenko AG The insulin receptor-related receptor (IRR), an orphan receptor tyrosine kinase of the insulin receptor family, can be activated by alkaline media both in vitro and in vivo at pH >7.9. The alkali-sensing property of IRR is conserved in frog, mouse, and human. IRR activation is specific, dose-dependent and quickly reversible and demonstrates positive cooperativity. It also triggers receptor conformational changes and elicits intracellular signaling. The pH sensitivity of IRR is primarily defined by its L1F extracellular domains. IRR is predominantly expressed in organs... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962284 Tue, 07 Jun 2011 23:00:00 +0100 4962284 http://www.medworm.com/index.php?rid=4962283&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641550%26dopt%3DAbstract Authors: Zhang J, Guan Z, Murphy AN, Wiley SE, Perkins GA, Worby CA, Engel JL, Heacock P, Nguyen OK, Wang JH, Raetz CR, Dowhan W, Dixon JE PTPMT1 was the first protein tyrosine phosphatase found localized to the mitochondria, but its biological function was unknown. Herein, we demonstrate that whole body deletion of Ptpmt1 in mice leads to embryonic lethality, suggesting an indispensable role for PTPMT1 during development. Ptpmt1 deficiency in mouse embryonic fibroblasts compromises mitochondrial respiration and results in abnormal mitochondrial morphology. Lipid analysis of Ptpmt1-deficient fibroblasts reveals an accumulation of phosphatidylglycerophosphate (PGP) along with a concomitant decrease in phosphatidylglycerol. PGP is an essential intermediate in the biosynthetic pathway of... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962283 Tue, 07 Jun 2011 23:00:00 +0100 4962283 http://www.medworm.com/index.php?rid=4962282&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641551%26dopt%3DAbstract Authors: Tang D, Kang R, Livesey KM, Kroemer G, Billiar TR, Van Houten B, Zeh HJ, Lotze MT Mitochondria are organelles centrally important for bioenergetics as well as regulation of apoptotic death in eukaryotic cells. High-mobility group box 1 (HMGB1), an evolutionarily conserved chromatin-associated protein which maintains nuclear homeostasis, is also a critical regulator of mitochondrial function and morphology. We show that heat shock protein beta-1 (HSPB1 or HSP27) is the downstream mediator of this effect. Disruption of the HSPB1 gene in embryonic fibroblasts with wild-type HMGB1 recapitulates the mitochondrial fragmentation, deficits in mitochondrial respiration, and adenosine triphosphate (ATP) synthesis observed with targeted deletion of HMGB1. Forced expression of HSPB1 rever... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962282 Tue, 07 Jun 2011 23:00:00 +0100 4962282 http://www.medworm.com/index.php?rid=4962281&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641552%26dopt%3DAbstract Authors: Acin-Perez R, Gatti DL, Bai Y, Manfredi G Rapid regulation of oxidative phosphorylation is crucial for mitochondrial adaptation to swift changes in fuels availability and energy demands. An intramitochondrial signaling pathway regulates cytochrome oxidase (COX), the terminal enzyme of the respiratory chain, through reversible phosphorylation. We find that PKA-mediated phosphorylation of a COX subunit dictates mammalian mitochondrial energy fluxes and identify the specific residue (S58) of COX subunit IV-1 (COXIV-1) that is involved in this mechanism of metabolic regulation. Using protein mutagenesis, molecular dynamics simulations, and induced fit docking, we show that mitochondrial energy metabolism regulation by phosphorylation of COXIV-1 is coupled with prevention of COX al... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962281 Tue, 07 Jun 2011 23:00:00 +0100 4962281 http://www.medworm.com/index.php?rid=4962280&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641553%26dopt%3DAbstract Authors: Könner AC, Hess S, Tovar S, Mesaros A, Sánchez-Lasheras C, Evers N, Verhagen LA, Brönneke HS, Kleinridders A, Hampel B, Kloppenburg P, Brüning JC Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962280 Tue, 07 Jun 2011 23:00:00 +0100 4962280 http://www.medworm.com/index.php?rid=4962279&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641554%26dopt%3DAbstract Authors: Potthoff MJ, Boney-Montoya J, Choi M, He T, Sunny NE, Satapati S, Suino-Powell K, Xu HE, Gerard RD, Finck BN, Burgess SC, Mangelsdorf DJ, Kliewer SA Regulation of hepatic carbohydrate homeostasis is crucial for maintaining energy balance in the face of fluctuating nutrient availability. Here, we show that the hormone fibroblast growth factor 15/19 (FGF15/19), which is released postprandially from the small intestine, inhibits hepatic gluconeogenesis, like insulin. However, unlike insulin, which peaks in serum 15 min after feeding, FGF15/19 expression peaks approximately 45 min later, when bile acid concentrations increase in the small intestine. FGF15/19 blocks the expression of genes involved in gluconeogenesis through a mechanism involving the dephosphorylation and inacti... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962279 Tue, 07 Jun 2011 23:00:00 +0100 4962279 http://www.medworm.com/index.php?rid=4962278&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21641555%26dopt%3DAbstract Authors: Ahmadian M, Abbott MJ, Tang T, Hudak CS, Kim Y, Bruss M, Hellerstein MK, Lee HY, Samuel VT, Shulman GI, Wang Y, Duncan RE, Kang C, Sul HS While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4962278 Tue, 07 Jun 2011 23:00:00 +0100 4962278 http://www.medworm.com/index.php?rid=4814320&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531329%26dopt%3DAbstract Authors: Dumas ME The microbiome heavily influences the metabolism of its host. In this issue of Cell Metabolism, Donohoe and colleagues demonstrate that microbial butyrate, used as a fuel metabolite, prevents autophagy in colonocytes, showing that the microbial-mammalian metabolic axis goes beyond simple metabolism. PMID: 21531329 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814320 Tue, 03 May 2011 23:00:00 +0100 4814320 http://www.medworm.com/index.php?rid=4814319&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531330%26dopt%3DAbstract Authors: Shah SH, Svetkey LP, Newgard CB Type 2 diabetes is an epidemic disease worldwide, but it is difficult to predict its appearance in the general population. A recent study demonstrates that circulating concentrations of a small group of essential amino acids predict risk for diabetes, contributing to a recent resurgence of interest in these common analytes. PMID: 21531330 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814319 Tue, 03 May 2011 23:00:00 +0100 4814319 http://www.medworm.com/index.php?rid=4814318&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531331%26dopt%3DAbstract Authors: Bartness TJ The function of dorsomedial hypothalamic neuropeptide Y (NPY) in energy balance has largely been restricted to lactation-induced hyperphagia. In this issue, Chao et al. (2011) expand this role to include inhibition of both brown fat thermogenesis and conversion of white-to-brown adipocytes in a white fat depot, resulting in reduced energy expenditure. PMID: 21531331 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814318 Tue, 03 May 2011 23:00:00 +0100 4814318 http://www.medworm.com/index.php?rid=4814317&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531332%26dopt%3DAbstract Authors: Singh R, Cuervo AM Autophagy mediates the degradation of cellular components in lysosomes, assuring removal of altered or dysfunctional proteins and organelles. Autophagy is not only activated in response to cellular damage; in fact, one of its strongest and better-characterized stimuli is starvation. Activation of autophagy when nutrients are scarce allows cells to reutilize their own constituents for energy. Besides protein breakdown, autophagy also contributes to the mobilization of diverse cellular energy stores. This recently discovered interplay between autophagy and lipid and carbohydrate metabolism reveals the existence of a dynamic feedback between autophagy and cellular energy balance. PMID: 21531332 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814317 Tue, 03 May 2011 23:00:00 +0100 4814317 http://www.medworm.com/index.php?rid=4814316&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531333%26dopt%3DAbstract Authors: Takahashi Y, Daitoku H, Hirota K, Tamiya H, Yokoyama A, Kako K, Nagashima Y, Nakamura A, Shimada T, Watanabe S, Yamagata K, Yasuda K, Ishii N, Fukamizu A Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814316 Tue, 03 May 2011 23:00:00 +0100 4814316 http://www.medworm.com/index.php?rid=4814315&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531334%26dopt%3DAbstract Authors: Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM, Bunger MK, Bultman SJ The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phospho... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814315 Tue, 03 May 2011 23:00:00 +0100 4814315 http://www.medworm.com/index.php?rid=4814314&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531335%26dopt%3DAbstract Authors: Cámara Y, Asin-Cayuela J, Park CB, Metodiev MD, Shi Y, Ruzzenente B, Kukat C, Habermann B, Wibom R, Hultenby K, Franz T, Erdjument-Bromage H, Tempst P, Hallberg BM, Gustafsson CM, Larsson NG Precise control of mitochondrial DNA gene expression is critical for regulation of oxidative phosphorylation capacity in mammals. The MTERF protein family plays a key role in this process, and its members have been implicated in regulation of transcription initiation and site-specific transcription termination. We now demonstrate that a member of this family, MTERF4, directly controls mitochondrial ribosomal biogenesis and translation. MTERF4 forms a stoichiometric complex with the ribosomal RNA methyltransferase NSUN4 and is necessary for recruitment of this factor to the large ribosomal... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814314 Tue, 03 May 2011 23:00:00 +0100 4814314 http://www.medworm.com/index.php?rid=4814313&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531336%26dopt%3DAbstract Authors: Im SS, Yousef L, Blaschitz C, Liu JZ, Edwards RA, Young SG, Raffatellu M, Osborne TF We show that mice with a targeted deficiency in the gene encoding the lipogenic transcription factor SREBP-1a are resistant to endotoxic shock and systemic inflammatory response syndrome induced by cecal ligation and puncture (CLP). When macrophages from the mutant mice were challenged with bacterial lipopolysaccharide, they failed to activate lipogenesis as well as two hallmark inflammasome functions, activation of caspase-1 and secretion of IL-1β. We show that SREBP-1a activates not only genes required for lipogenesis in macrophages but also the gene encoding Nlrp1a, which is a core inflammasome component. Thus, SREBP-1a links lipid metabolism to the innate immune response, which supports o... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814313 Tue, 03 May 2011 23:00:00 +0100 4814313 http://www.medworm.com/index.php?rid=4814312&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531337%26dopt%3DAbstract Authors: Endo Y, Suzuki M, Yamada H, Horita S, Kunimi M, Yamazaki O, Shirai A, Nakamura M, Iso-O N, Li Y, Hara M, Tsukamoto K, Moriyama N, Kudo A, Kawakami H, Yamauchi T, Kubota N, Kadowaki T, Kume H, Enomoto Y, Homma Y, Seki G, Fujita T Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor γ (PPARγ). However, the use of TZDs is associated with plasma volume expansion through a mechanism that remains to be clarified. Here we showed that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from the renal proximal tubule in vitro and in vivo. TZD-induced transport stimulation is dependent on PPARγ-Src-EGFR-ERK and observed in rat, rabbit and human, but not in mouse proximal tubules where Src... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814312 Tue, 03 May 2011 23:00:00 +0100 4814312 http://www.medworm.com/index.php?rid=4814311&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531338%26dopt%3DAbstract Authors: Rousso-Noori L, Knobler H, Levy-Apter E, Kuperman Y, Neufeld-Cohen A, Keshet Y, Akepati VR, Klinghoffer RA, Chen A, Elson A Molecular-level understanding of body weight control is essential for combating obesity. We show that female mice lacking tyrosine phosphatase epsilon (RPTPe) are protected from weight gain induced by high-fat food, ovariectomy, or old age and exhibit increased whole-body energy expenditure and decreased adiposity. RPTPe-deficient mice, in particular males, exhibit improved glucose homeostasis. Female nonobese RPTPe-deficient mice are leptin hypersensitive and exhibit reduced circulating leptin concentrations, suggesting that RPTPe inhibits hypothalamic leptin signaling in vivo. Leptin hypersensitivity persists in aged, ovariectomized, and high-fat-fed R... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814311 Tue, 03 May 2011 23:00:00 +0100 4814311 http://www.medworm.com/index.php?rid=4814310&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531339%26dopt%3DAbstract Authors: Chao PT, Yang L, Aja S, Moran TH, Bi S Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the t... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814310 Tue, 03 May 2011 23:00:00 +0100 4814310 http://www.medworm.com/index.php?rid=4814307&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531340%26dopt%3DAbstract Authors: Lam DD, Leinninger GM, Louis GW, Garfield AS, Marston OJ, Leshan RL, Scheller EL, Christensen L, Donato J, Xia J, Evans ML, Elias C, Dalley JW, Burdakov DI, Myers MG, Heisler LK Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmenta... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814307 Tue, 03 May 2011 23:00:00 +0100 4814307 http://www.medworm.com/index.php?rid=4814302&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531341%26dopt%3DAbstract Authors: Zhou Z, Subramanian P, Sevilmis G, Globke B, Soehnlein O, Karshovska E, Megens R, Heyll K, Chun J, Saulnier-Blache JS, Reinholz M, van Zandvoort M, Weber C, Schober A Oxidatively modified low-density lipoprotein (oxLDL) plays a key role in the initiation of atherosclerosis by increasing monocyte adhesion. The mechanism that is responsible for the oxLDL-induced atherogenic monocyte recruitment in vivo, however, still remains unknown. Oxidation of LDL generates lysophosphatidylcholine, which is the main substrate for the lysophosphatidic acid (LPA) generating enzyme autotaxin. We show that oxLDL requires endothelial LPA receptors and autotaxin to elicit CXCL1-dependent arterial monocyte adhesion. Unsaturated LPA releases endothelial CXCL1, which is subsequently immobilized on t... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814302 Tue, 03 May 2011 23:00:00 +0100 4814302 http://www.medworm.com/index.php?rid=4814298&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21531342%26dopt%3DAbstract Authors: Wiederkehr A, Szanda G, Akhmedov D, Mataki C, Heizmann CW, Schoonjans K, Pozzan T, Spät A, Wollheim CB Mitochondrial Ca(2+) signals have been proposed to accelerate oxidative metabolism and ATP production to match Ca(2+)-activated energy-consuming processes. Efforts to understand the signaling role of mitochondrial Ca(2+) have been hampered by the inability to manipulate matrix Ca(2+) without directly altering cytosolic Ca(2+). We were able to selectively buffer mitochondrial Ca(2+) rises by targeting the Ca(2+)-binding protein S100G to the matrix. We find that matrix Ca(2+) controls signal-dependent NAD(P)H formation, respiration, and ATP changes in intact cells. Furthermore, we demonstrate that matrix Ca(2+) increases are necessary for the amplification of sustained glucose... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4814298 Tue, 03 May 2011 23:00:00 +0100 4814298 http://www.medworm.com/index.php?rid=4706546&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459315%26dopt%3DAbstract Authors: Handschin C, Spiegelman BM PMID: 21459315 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706546 Tue, 05 Apr 2011 23:00:00 +0100 4706546 http://www.medworm.com/index.php?rid=4706545&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459316%26dopt%3DAbstract Authors: Zechner C, Leone TC, Kelly DP PMID: 21459316 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706545 Tue, 05 Apr 2011 23:00:00 +0100 4706545 http://www.medworm.com/index.php?rid=4706544&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459317%26dopt%3DAbstract Authors: Luo X, Kraus WL In two related papers in this issue, Bai et al. (2011a, 2011b) observe that PARP-1- or PARP-2-deficient mice show increased energy expenditure and protection against diet-induced obesity. This metabolic phenotype is achieved, in part, through SIRT1 activation, either by increasing NAD(+) levels or by promoting SIRT1 expression. PMID: 21459317 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706544 Tue, 05 Apr 2011 23:00:00 +0100 4706544 http://www.medworm.com/index.php?rid=4706542&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459318%26dopt%3DAbstract Authors: Gallagher EJ, Leroith D GH, IGF-1, and insulin are emerging as important and independent mediators of tumor development and aging. Two recent studies report that humans with GH-receptor deficiency are protected from developing cancer through alterations in GH, IGF-1, and insulin signaling, decreasing the susceptibility of cells to DNA damage and abnormal proliferation. PMID: 21459318 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706542 Tue, 05 Apr 2011 23:00:00 +0100 4706542 http://www.medworm.com/index.php?rid=4706541&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459319%26dopt%3DAbstract Authors: Ferrer J Glucose stimulates insulin secretion in β cells, which sense glucose concentrations through signals derived from glycolytic metabolism. In this issue of Cell Metabolism, Dor and colleagues (Porat et al., 2011) combine genetic, transplantation, and pharmacologic approaches to show that glucose also stimulates β cell proliferation through similar metabolic signals, providing a new framework to develop therapeutics for diabetes. PMID: 21459319 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706541 Tue, 05 Apr 2011 23:00:00 +0100 4706541 http://www.medworm.com/index.php?rid=4706539&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459320%26dopt%3DAbstract Authors: Brunet A Cutting down calories prolongs life, but how this works remains largely unknown. A recent study in Nature (Mair et al., 2011) shows that life span extension triggered by the energy-sensing protein kinase AMPK is mediated by an evolutionarily conserved transcriptional circuit involving CRTC-1 and CREB. PMID: 21459320 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706539 Tue, 05 Apr 2011 23:00:00 +0100 4706539 http://www.medworm.com/index.php?rid=4706538&cid=s_35395_171_f&fid=35395&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459321%26dopt%3DAbstract Authors: Murphy MP, Holmgren A, Larsson NG, Halliwell B, Chang CJ, Kalyanaraman B, Rhee SG, Thornalley PJ, Partridge L, Gems D, Nyström T, Belousov V, Schumacker PT, Winterbourn CC Reactive oxygen species are not only harmful agents that cause oxidative damage in pathologies, they also have important roles as regulatory agents in a range of biological phenomena. The relatively recent development of this more nuanced view presents a challenge to the biomedical research community on how best to assess the significance of reactive oxygen species and oxidative damage in biological systems. Considerable progress is being made in addressing these issues, and here we survey some recent developments for those contemplating research in this area. PMID: 21459321 [PubMed - in process] (Sourc... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=4706538 Tue, 05 Apr 2011 23:00:00 +0100 4706538