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. Sun, 21 Mar 2010 17:33:07 +0100 http://www.medworm.com/index.php?rid=3331514&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%3D20197047%26dopt%3DAbstract Authors: Brasaemle DL The complex process of lipolysis mobilizes fatty acids from adipocyte triglyceride stores for energy production in muscle and other organs during fasting and exercise. In this issue of Cell Metabolism, Yang, et al. identify G0S2 as a regulator of the key enzyme, adipose triglyceride lipase. PMID: 20197047 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331514 Wed, 03 Mar 2010 00:00:00 +0100 3331514 http://www.medworm.com/index.php?rid=3331513&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%3D20197048%26dopt%3DAbstract Authors: Novack DV Systemic glucose homeostasis is primarily regulated by insulin, which targets liver, fat, and skeletal muscle cells, setting up important feedback loops. New studies now show that the osteoblast also has a significant role in modulating systemic insulin responses, via the insulin-regulated transcription factor FOXO1 and the hormone osteocalcin. PMID: 20197048 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331513 Wed, 03 Mar 2010 00:00:00 +0100 3331513 http://www.medworm.com/index.php?rid=3331490&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%3D20197049%26dopt%3DAbstract Authors: Kirstein-Miles J, Morimoto RI The unfolded protein response (UPR(mt)) rebalances mitochondrial protein homeostasis upon proteotoxic perturbations. Haynes et al. (2010) show that this retrograde stress signal is based on efflux of peptides derived from damaged proteins from the mitochondrial matrix to the cytosol; this initiates downstream protective responses in the nucleus to restore cellular balance. PMID: 20197049 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331490 Wed, 03 Mar 2010 00:00:00 +0100 3331490 http://www.medworm.com/index.php?rid=3331468&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%3D20197050%26dopt%3DAbstract Authors: Ashcroft FM The discovery that their neonatal diabetes is caused by gain-of-function mutations in the K(ATP) channel has enabled many patients to switch from insulin to oral sulphonylurea drugs. Here, I review molecular, physiological, and clinical features of this change in therapy. PMID: 20197050 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331468 Wed, 03 Mar 2010 00:00:00 +0100 3331468 http://www.medworm.com/index.php?rid=3331467&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%3D20197051%26dopt%3DAbstract Authors: Wei E, Ben Ali Y, Lyon J, Wang H, Nelson R, Dolinsky VW, Dyck JR, Mitchell G, Korbutt GS, Lehner R Excessive accumulation of triacylglycerol in peripheral tissues is tightly associated with obesity and has been identified as an independent risk factor for insulin resistance, type 2 diabetes, and cardiovascular complications. Here we show that ablation of carboxylesterase 3 (Ces3)/triacylglycerol hydrolase (TGH) expression in mice (Tgh(-/-)) results in decreased plasma triacylglycerol, apolipoprotein B, and fatty acid levels in both fasted and fed states. Despite the attenuation of very low-density lipoprotein secretion, TGH deficiency does not increase hepatic triacylglycerol levels. Tgh(-/-) mice exhibit increased food intake, respiratory quotient, and energy expenditure with... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331467 Wed, 03 Mar 2010 00:00:00 +0100 3331467 http://www.medworm.com/index.php?rid=3331466&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%3D20197052%26dopt%3DAbstract Authors: Yang X, Lu X, Lombès M, Rha GB, Chi YI, Guerin TM, Smart EJ, Liu J Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G(0)/G(1) switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331466 Wed, 03 Mar 2010 00:00:00 +0100 3331466 http://www.medworm.com/index.php?rid=3331465&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%3D20197053%26dopt%3DAbstract Authors: Hondares E, Rosell M, Gonzalez FJ, Giralt M, Iglesias R, Villarroya F Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPARalpha null neonates, and is mimicked by treatment with the PPARalpha activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and in... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331465 Wed, 03 Mar 2010 00:00:00 +0100 3331465 http://www.medworm.com/index.php?rid=3331464&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%3D20197054%26dopt%3DAbstract Authors: Cantó C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, Zierath JR, Auwerx J During fasting and after exercise, skeletal muscle efficiently switches from carbohydrate to lipid as the main energy source to preserve glycogen stores and blood glucose levels for glucose-dependent tissues. Skeletal muscle cells sense this limitation in glucose availability and transform this information into transcriptional and metabolic adaptations. Here we demonstrate that AMPK acts as the prime initial sensor that translates this information into SIRT1-dependent deacetylation of the transcriptional regulators PGC-1alpha and FOXO1, culminating in the transcriptional modulation of mitochondrial and lipid utilization genes. Deficient AMPK activity compromises SIRT1-dependent responses to... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331464 Wed, 03 Mar 2010 00:00:00 +0100 3331464 http://www.medworm.com/index.php?rid=3331463&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%3D20197055%26dopt%3DAbstract Authors: Sopasakis VR, Liu P, Suzuki R, Kondo T, Winnay J, Tran TT, Asano T, Smyth G, Sajan MP, Farese RV, Kahn CR, Zhao JJ The class I(A) phosphatidylinsositol 3-kinases (PI3Ks) form a critical node in the insulin metabolic pathway; however, the precise roles of the different isoforms of this enzyme remain elusive. Using tissue-specific gene inactivation, we demonstrate that p110alpha catalytic subunit of PI3K is a key mediator of insulin metabolic actions in the liver. Thus, deletion of p110alpha in liver results in markedly blunted insulin signaling with decreased generation of PIP(3) and loss of insulin activation of Akt, defects that could not be rescued by overexpression of p110beta. As a result, mice with hepatic knockout of p110alpha display reduced insulin sensitivity, impaire... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331463 Wed, 03 Mar 2010 00:00:00 +0100 3331463 http://www.medworm.com/index.php?rid=3331462&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%3D20197056%26dopt%3DAbstract Authors: Shi Y, Oury F, Yadav VK, Wess J, Liu XS, Guo XE, Murshed M, Karsenty G Bone remodeling is regulated by various neuronal inputs, including sympathetic tone, which is known to inhibit bone mass accrual. This aspect of sympathetic nervous system function raises the prospect that the other arm of the autonomic nervous system, the parasympathetic nervous system, may also affect bone remodeling. Here, we use various mutant mouse strains, each lacking one of the muscarinic receptors that mediate parasympathetic activity, to show that the parasympathetic nervous system acting through the M(3) muscarinic receptor is a positive regulator of bone mass accrual, increasing bone formation and decreasing bone resorption. Gene expression studies, cell-specific gene deletion experiments, and a... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3331462 Wed, 03 Mar 2010 00:00:00 +0100 3331462 http://www.medworm.com/index.php?rid=3263354&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%3D20142097%26dopt%3DAbstract Authors: Coll AP BRS-3 is an orphan G protein coupled receptor highly expressed in the brain. Pharmacological studies in this issue (Guan et al., 2010) further support a role for this receptor in energy homeostasis and show that the BRS-3 agonist Bag-1 effectively causes weight loss by decreasing food intake and increasing metabolic rate. PMID: 20142097 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263354 Wed, 03 Feb 2010 00:00:00 +0100 3263354 http://www.medworm.com/index.php?rid=3263353&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%3D20142098%26dopt%3DAbstract Authors: Eckel-Mahan K, Sassone-Corsi P While Cry proteins are necessary for circadian rhythmicity, they now appear to play a seminal role in blood pressure regulation. In a recent issue of Nature Medicine, Doi et al., 2009 show how the circadian clock may use Cry proteins to protect from salt-sensitive hypertension. PMID: 20142098 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263353 Wed, 03 Feb 2010 00:00:00 +0100 3263353 http://www.medworm.com/index.php?rid=3263352&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%3D20142099%26dopt%3DAbstract Authors: Yamada E, Pessin JE, Kurland IJ, Schwartz GJ, Bastie CC Fyn null mice display reduced adiposity associated with increased fatty acid oxidation, energy expenditure, and activation of the AMP-dependent protein kinase (AMPK) in skeletal muscle and adipose tissue. The acute pharmacological inhibition of Fyn kinase activity with SU6656 in wild-type mice reproduces these metabolic effects and induced a specific reduction in fat mass with no change in lean mass. LKB1, the main upstream AMPK kinase (AMPKK) in peripheral tissues, was redistributed from the nucleus into the cytoplasm of cells treated with SU6656 and in cells expressing a kinase-deficient, but not a constitutively kinase-active, Fyn mutant. Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residue... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263352 Wed, 03 Feb 2010 00:00:00 +0100 3263352 http://www.medworm.com/index.php?rid=3263351&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%3D20142100%26dopt%3DAbstract Authors: Becker L, Gharib SA, Irwin AD, Wijsman E, Vaisar T, Oram JF, Heinecke JW Cholesteryl ester accumulation by macrophages is a critical early event in atherogenesis. To test the hypothesis that sterol loading promotes foam cell formation and vascular disease by perturbing a network of interacting proteins, we used a global approach to identify proteins that are differentially expressed when macrophages are loaded with cholesterol in vivo. Our analysis revealed a sterol-responsive network that is highly enriched in proteins with known physical interactions, established roles in vesicular transport, and demonstrated atherosclerotic phenotypes in mice. Pharmacologic intervention with a statin or rosiglitazone and use of mice deficient in LDL receptor or apolipoprotein E implicated t... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263351 Wed, 03 Feb 2010 00:00:00 +0100 3263351 http://www.medworm.com/index.php?rid=3263350&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%3D20142101%26dopt%3DAbstract Authors: Ambrogini E, Almeida M, Martin-Millan M, Paik JH, Depinho RA, Han L, Goellner J, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC Aging increases oxidative stress and osteoblast apoptosis and decreases bone mass, whereas forkhead box O (FoxO) transcription factors defend against oxidative stress by activating genes involved in free radical scavenging and apoptosis. Conditional deletion of FoxO1, FoxO3, and FoxO4 in 3-month-old mice resulted in an increase in oxidative stress in bone and osteoblast apoptosis and a decrease in the number of osteoblasts, the rate of bone formation, and bone mass at cancellous and cortical sites. The effect of the deletion on osteoblast apoptosis was cell autonomous and resulted from oxidative stress. Conversely, overexpression of a FoxO3 transgen... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263350 Wed, 03 Feb 2010 00:00:00 +0100 3263350 http://www.medworm.com/index.php?rid=3263349&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%3D20142102%26dopt%3DAbstract Authors: Rached MT, Kode A, Xu L, Yoshikawa Y, Paik JH, Depinho RA, Kousteni S Osteoporosis, a disease of low bone mass, is associated with decreased osteoblast numbers and increased levels of oxidative stress within osteoblasts. Since transcription factors of the FoxO family confer stress resistance, we investigated their potential impact on skeletal integrity. Here we employ cell-specific deletion and molecular analyses to show that, among the three FoxO proteins, only FoxO1 is required for proliferation and redox balance in osteoblasts and thereby controls bone formation. FoxO1 regulation of osteoblast proliferation occurs through its interaction with ATF4, a transcription factor regulating amino acid import, as well as through its regulation of a stress-dependent pathway influencin... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263349 Wed, 03 Feb 2010 00:00:00 +0100 3263349 http://www.medworm.com/index.php?rid=3263348&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%3D20142103%26dopt%3DAbstract Authors: Guo J, Liu M, Yang D, Bouxsein ML, Saito H, Galvin RJ, Kuhstoss SA, Thomas CC, Schipani E, Baron R, Bringhurst FR, Kronenberg HM Parathyroid hormone (PTH) suppresses Dickkopf 1 (Dkk1) expression in osteoblasts. To determine whether this suppression is essential for PTH-mediated Wnt signaling and bone formation, we examined mice that overexpress Dkk1 in osteoblasts (Dkk1 mice). Dkk1 mice were osteopenic due to abnormal osteoblast and osteoclast activity. When fed a low-calcium diet, and in two other models of hyperparathyroidism, these mice failed to develop the peritrabecular stromal cell response ("osteitis fibrosis") and new bone formation seen in wild-type mice. Despite these effects of Dkk1 overexpression, PTH still activated Wnt signaling in Dkk1 mice and in osteoblastic ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3263348 Wed, 03 Feb 2010 00:00:00 +0100 3263348 http://www.medworm.com/index.php?rid=3213275&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%3D20096642%26dopt%3DAbstract Authors: Guan XM, Chen H, Dobbelaar PH, Dong Y, Fong TM, Gagen K, Gorski J, He S, Howard AD, Jian T, Jiang M, Kan Y, Kelly TM, Kosinski J, Lin LS, Liu J, Marsh DJ, Metzger JM, Miller R, Nargund RP, Palyha O, Shearman L, Shen Z, Stearns R, Strack AM, Stribling S, Tang YS, Wang SP, White A, Yu H, Reitman ML Bombesin receptor subtype 3 (BRS-3) is a G protein coupled receptor whose natural ligand is unknown. We developed potent, selective agonist (Bag-1, Bag-2) and antagonist (Bantag-1) ligands to explore BRS-3 function. BRS-3-binding sites were identified in the hypothalamus, caudal brainstem, and several midbrain nuclei that harbor monoaminergic cell bodies. Antagonist administration increased food intake and body weight, whereas agonists increased metabolic rate and reduced food intake ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3213275 Wed, 20 Jan 2010 00:00:00 +0100 3213275 http://www.medworm.com/index.php?rid=3196674&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%3D20085728%26dopt%3DAbstract Authors: Kushner JA, Weir GC, Bonner-Weir S Although pancreatic beta cells are known to expand by self-renewal in postnatal life, contribution by ductal progenitors remains vigorously debated. In a recent issue of Developmental Cell, Jorge Ferrer and colleagues report lineage tracing studies that challenge the ductal origin hypothesis (Solar et al., 2009). PMID: 20085728 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3196674 Wed, 06 Jan 2010 00:00:00 +0100 3196674 http://www.medworm.com/index.php?rid=3196673&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%3D20085729%26dopt%3DAbstract Authors: Wess J Various members of the G protein-coupled receptor (GPCR) superfamily are known to modulate the release of insulin from pancreatic beta cells. Rosengren and colleagues have recently provided convincing evidence for a role of increased expression of the alpha(2A)-adrenoceptor in beta cells in the pathogenesis of type 2 diabetes. PMID: 20085729 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3196673 Wed, 06 Jan 2010 00:00:00 +0100 3196673 http://www.medworm.com/index.php?rid=3196671&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%3D20085731%26dopt%3DAbstract Authors: Teleman AA Insulin signaling is a key regulator of metabolism and tissue growth in animals. Recent work in Cell (Hyun et al., 2009) defines two conserved components of the insulin pathway: a microRNA and the protein USH/FOG2. PMID: 20085731 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3196671 Wed, 06 Jan 2010 00:00:00 +0100 3196671 http://www.medworm.com/index.php?rid=3196670&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%3D20085732%26dopt%3DAbstract Authors: Edgar D, Larsson NG, Trifunovic A PMID: 20085732 [PubMed - as supplied by publisher] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3196670 Wed, 06 Jan 2010 00:00:00 +0100 3196670 http://www.medworm.com/index.php?rid=3196672&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%3D20085730%26dopt%3DAbstract Authors: Cantó C, Auwerx J The link between Akt activation and gluconeogenic repression remains unclear, despite many years of investigation and remarkable progress. Rodgers and colleagues now introduce us to the Clk2 kinase, an Akt substrate that can directly phosphorylate and inhibit PGC-1alpha, blunting hepatic glucose production. PMID: 20085730 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3196672 Fri, 01 Jan 2010 00:00:00 +0100 3196672 http://www.medworm.com/index.php?rid=3179327&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%3D20074524%26dopt%3DAbstract Authors: Hedbacker K, Birsoy K, Wysocki RW, Asilmaz E, Ahima RS, Farooqi IS, Friedman JM We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma glucose and insulin concentration. We found that a leptin dose of 12.5 ng/hr significantly lowers blood glucose and that 25 ng/hr of leptin normalizes plasma glucose and insulin without significantly reducing body weight, establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 (IGFBP2) as being regulated by leptin with a similarly high potency. Overexpression of IGFBP2 by an adenovirus reversed diabet... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179327 Fri, 01 Jan 2010 00:00:00 +0100 3179327 http://www.medworm.com/index.php?rid=3179326&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%3D20074525%26dopt%3DAbstract Authors: Rodgers JT, Haas W, Gygi SP, Puigserver P Dynamic regulation of insulin signaling and metabolic gene expression is critical to nutrient homeostasis; dysregulation of these pathways is widely implicated in insulin resistance and other disease states. Though the metabolic effects of insulin are well established, the components linking insulin signal transduction to a metabolic response are not as well understood. Here, we show that Cdc2-like kinase 2 (Clk2) is an insulin-regulated suppressor of hepatic gluconeogenesis and glucose output. Clk2 protein levels and kinase activity are induced as part of the hepatic refeeding response by the insulin/Akt pathway. Clk2 directly phosphorylates the SR domain on PGC-1alpha, resulting in repression of gluconeogenic gene expression and hepa... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179326 Fri, 01 Jan 2010 00:00:00 +0100 3179326 http://www.medworm.com/index.php?rid=3179325&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%3D20074526%26dopt%3DAbstract Authors: Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179325 Fri, 01 Jan 2010 00:00:00 +0100 3179325 http://www.medworm.com/index.php?rid=3179324&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%3D20074527%26dopt%3DAbstract Authors: Cretenet G, Le Clech M, Gachon F The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose, and xenobiotic metabolism. Impairment of this rhythm has been shown to lead to diverse pathologies, including metabolic syndrome. Currently, it is supposed that the circadian clock regulates metabolism mostly by regulating expression of liver enzymes at the transcriptional level. Here, we show that the circadian clock also controls hepatic metabolism by synchronizing a secondary 12 hr period rhythm characterized by rhythmic activation of the IRE1alpha pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock and provokes deregulation of endoplasmic reticulum-localized enzymes. This leads to impaired lip... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179324 Fri, 01 Jan 2010 00:00:00 +0100 3179324 http://www.medworm.com/index.php?rid=3179323&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%3D20074528%26dopt%3DAbstract Authors: Alekseev AE, Reyes S, Yamada S, Hodgson-Zingman DM, Sattiraju S, Zhu Z, Sierra A, Gerbin M, Coetzee WA, Goldhamer DJ, Terzic A, Zingman LV Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K(+) (K(ATP)) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of K(ATP) channel function provoked, under conditions of unaltered locomotor activity and blood substrate availability, an extra energy cost of cardiac and skeletal muscle performance. Inefficient fuel metabolism in K(ATP) channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179323 Fri, 01 Jan 2010 00:00:00 +0100 3179323 http://www.medworm.com/index.php?rid=3179322&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%3D20074529%26dopt%3DAbstract Authors: Hoehn KL, Turner N, Swarbrick MM, Wilks D, Preston E, Phua Y, Joshi H, Furler SM, Larance M, Hegarty BD, Leslie SJ, Pickford R, Hoy AJ, Kraegen EW, James DE, Cooney GJ Activation of AMP-activated protein kinase (AMPK) is thought to convey many of the beneficial effects of exercise via its inhibitory effect on acetyl-CoA carboxylase 2 (ACC2) and promotion of fatty acid oxidation. Hence, AMPK and ACC have become major drug targets for weight loss and improved insulin action. However, it remains unclear whether or how activation of the fatty acid oxidation pathway without a concomitant increase in energy expenditure could be beneficial. Here, we have used either pharmacological (administration of the AMPK agonist 5(') aminoimidazole-4-carboxamide-riboside) or genetic means (mutat... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179322 Fri, 01 Jan 2010 00:00:00 +0100 3179322 http://www.medworm.com/index.php?rid=3179321&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%3D20074530%26dopt%3DAbstract Authors: Hayes MR, Skibicka KP, Leichner TM, Guarnieri DJ, DiLeone RJ, Bence KK, Grill HJ Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased s... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179321 Fri, 01 Jan 2010 00:00:00 +0100 3179321 http://www.medworm.com/index.php?rid=3179320&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%3D20074531%26dopt%3DAbstract Authors: Copps KD, Hancer NJ, Opare-Ado L, Qiu W, Walsh C, White MF Phosphorylation of the insulin receptor substrates (Irs) on serine residues-typified by Ser307 of rodent Irs1-is thought to mediate insulin resistance. To determine whether Ser307 negatively regulates Irs1 in vivo, we generated knockin mice in which Ser307 (human Ser312) was replaced with alanine (A/A). Unexpectedly, A/A mice that were fed a high-fat diet developed more severe insulin resistance than control mice, accompanied by enhanced pancreatic compensation and impaired muscle insulin signaling. Chow-fed mice whose livers lacked Irs2 but retained a single knockin allele (A/lox::LKO2) were profoundly insulin resistant (versus +/lox::LKO2 mice), and their hepatocytes showed impaired insulin signaling ex vivo. Similar... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3179320 Fri, 01 Jan 2010 00:00:00 +0100 3179320 http://www.medworm.com/index.php?rid=3042300&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%3D19945399%26dopt%3DAbstract Authors: Vermulst M, Wanagat J, Loeb LA PMID: 19945399 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042300 Tue, 01 Dec 2009 00:00:00 +0100 3042300 http://www.medworm.com/index.php?rid=3042299&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%3D19945400%26dopt%3DAbstract Authors: Kühnlein RP Dietary lipid digestion is critical for body fat storage control, but little is known about the regulation of genes involved in fat breakdown and absorption in the gastrointestinal tract. A Drosophila study (Sieber and Thummel, 2009 [this issue of Cell Metabolism]) now demonstrates that the orphan nuclear receptor DHR96 adjusts fat storage in flies by tuning gastric lipase expression. PMID: 19945400 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042299 Tue, 01 Dec 2009 00:00:00 +0100 3042299 http://www.medworm.com/index.php?rid=3042298&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%3D19945401%26dopt%3DAbstract Authors: Kühn LC Cells regulate iron homeostasis by posttranscriptional regulation of proteins responsible for iron uptake and storage. This requires RNA-binding activity of iron-regulatory proteins, IRP1 and IRP2. Two studies recently published in Science by Vashisht et al. (2009) and Salahudeen et al. (2009) reveal how cells adjust IRP2 activity. PMID: 19945401 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042298 Tue, 01 Dec 2009 00:00:00 +0100 3042298 http://www.medworm.com/index.php?rid=3042297&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%3D19945402%26dopt%3DAbstract Authors: Remedi MS, Nichols CG The role of metabolism-excitation coupling in insulin secretion has long been apparent, but in recent years, in parallel with studies of human hyperinsulinism and diabetes, genetic manipulation of proteins involved in glucose transport, metabolism, and excitability in mice has brought the central importance of this pathway into sharp relief. We focus on these animal studies and how they provide important insights into not only metabolic and electrical regulation of insulin secretion, but also downstream consequences of alterations in this pathway and the etiology and treatment of insulin-secretion diseases in humans. PMID: 19945402 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042297 Tue, 01 Dec 2009 00:00:00 +0100 3042297 http://www.medworm.com/index.php?rid=3042296&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%3D19945403%26dopt%3DAbstract Authors: Hoppa MB, Collins S, Ramracheya R, Hodson L, Amisten S, Zhang Q, Johnson P, Ashcroft FM, Rorsman P Long-term (72 hr) exposure of pancreatic islets to palmitate inhibited glucose-induced insulin secretion by >50% with first- and second-phase secretion being equally suppressed. This inhibition correlated with the selective impairment of exocytosis evoked by brief (action potential-like) depolarizations, whereas that evoked by long ( approximately 250 ms) stimuli was unaffected. Under normal conditions, Ca(2+) influx elicited by brief membrane depolarizations increases [Ca(2+)](i) to high levels within discrete microdomains and triggers the exocytosis of closely associated insulin granules. We found that these domains of localized Ca(2+) entry become dispersed by long-term (72... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042296 Tue, 01 Dec 2009 00:00:00 +0100 3042296 http://www.medworm.com/index.php?rid=3042295&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%3D19945404%26dopt%3DAbstract Authors: Shiuchi T, Haque MS, Okamoto S, Inoue T, Kageyama H, Lee S, Toda C, Suzuki A, Bachman ES, Kim YB, Sakurai T, Yanagisawa M, Shioda S, Imoto K, Minokoshi Y Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by activating the sympathetic nervous system. These effects of orexin were blunted in mice lacking beta-adrenergic receptors but were restored by forced expression of the beta(2)-adrenergic receptor in both myocytes and nonmyocyte cells of skeletal muscle. Orexin neurons are activate... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042295 Tue, 01 Dec 2009 00:00:00 +0100 3042295 http://www.medworm.com/index.php?rid=3042294&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%3D19945405%26dopt%3DAbstract This study provides insights into the regulation of dietary fat metabolism in Drosophila and demonstrates that the regulation of lipid metabolism is an ancestral function of the PXR/CAR/DHR96 nuclear receptor subfamily. PMID: 19945405 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042294 Tue, 01 Dec 2009 00:00:00 +0100 3042294 http://www.medworm.com/index.php?rid=3042293&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%3D19945406%26dopt%3DAbstract Authors: Sabio G, Cavanagh-Kyros J, Ko HJ, Jung DY, Gray S, Jun JY, Barrett T, Mora A, Kim JK, Davis RJ Nonalcoholic steatosis (fatty liver) is a major cause of liver dysfunction that is associated with insulin resistance and metabolic syndrome. The cJun NH(2)-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful for treatment of this disease. Indeed, mice with defects in JNK1 expression in adipose tissue are protected against hepatic steatosis. Here we report that mice with specific ablation of Jnk1 in hepatocytes exhibit glucose intolerance, insulin resistance, and hepatic steatosis. JNK1 therefore serves opposing actions in liver and adipose tissue to both promote and prevent hepatic steatosis. This... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042293 Tue, 01 Dec 2009 00:00:00 +0100 3042293 http://www.medworm.com/index.php?rid=3042292&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%3D19945407%26dopt%3DAbstract Authors: Erion DM, Ignatova ID, Yonemitsu S, Nagai Y, Chatterjee P, Weismann D, Hsiao JJ, Zhang D, Iwasaki T, Stark R, Flannery C, Kahn M, Carmean CM, Yu XX, Murray SF, Bhanot S, Monia BP, Cline GW, Samuel VT, Shulman GI In patients with poorly controlled type 2 diabetes mellitus (T2DM), hepatic insulin resistance and increased gluconeogenesis contribute to fasting and postprandial hyperglycemia. Since cAMP response element-binding protein (CREB) is a key regulator of gluconeogenic gene expression, we hypothesized that decreasing hepatic CREB expression would reduce fasting hyperglycemia in rodent models of T2DM. In order to test this hypothesis, we used a CREB-specific antisense oligonucleotide (ASO) to knock down CREB expression in liver. CREB ASO treatment dramatically reduced fasti... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042292 Tue, 01 Dec 2009 00:00:00 +0100 3042292 http://www.medworm.com/index.php?rid=3042291&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%3D19945408%26dopt%3DAbstract Authors: Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes for protein and organelle clearance. In skeletal muscle, both systems are under FoxO regulation and their excessive activation induces severe muscle loss. Although altered autophagy has been observed in various myopathies, the specific role of autophagy in skeletal muscle has not been determined by loss-of-function approaches. Here, we report that muscle-specific deletion of a crucial autophagy gene, Atg7, resulted in profound muscle atrophy and age-dependent decrease in force. Atg7 null muscles showed accumulation of abnormal mitochondria, sarcoplasmic reticulum distension, disorganizatio... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042291 Tue, 01 Dec 2009 00:00:00 +0100 3042291 http://www.medworm.com/index.php?rid=3042290&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%3D19945409%26dopt%3DAbstract This study demonstrates for the first time a cytoplasmic function for RIP140: to counteract insulin-stimulated glucose transporter 4 (GLUT4) membrane partitioning and glucose uptake in adipocytes. Cytoplasmic RIP140 interacts with the Akt substrate AS160, thereby impeding AS160 phosphorylation by Akt; this in turn reduces GLUT4 trafficking. This signal transduction pathway can be recapitulated in the epididymal adipocytes of diet-induced obese mice: nuclear PKCvarepsilon is activated, cytoplasmic RIP140 increases, and GLUT4 trafficking and glucose uptake are reduced. The data reveal a new, cytoplasmic function for RIP140 as a negative regulator of GLUT4 trafficking and glucose uptake, and shed insight into the regulation of basal and insulin-stimulated glucose disposal by a nuclear-initiat... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=3042290 Tue, 01 Dec 2009 00:00:00 +0100 3042290 http://www.medworm.com/index.php?rid=2963488&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%3D19883611%26dopt%3DAbstract Authors: Abate JP, Blackwell TK Insulin is essential for glucose homeostasis, but reducing its activity delays the aging process in model organisms. In this issue of Cell Metabolism, Lee et al. (2009) show how these effects of insulin signaling intersect when glucose is fed to C. elegans. PMID: 19883611 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963488 Sun, 01 Nov 2009 00:00:00 +0100 2963488 http://www.medworm.com/index.php?rid=2963487&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%3D19883612%26dopt%3DAbstract Authors: Low MJ Proopiomelanocortin (Pomc) neurons play a central role in energy homeostasis. Despite the complexity of Pomc posttranslational processing, regulation of Pomc gene expression often takes center stage. Complementary papers that zero in on distinct carboxypeptidases (Plum et al., 2009; Wallingford et al., 2009) now refocus the spotlight on regulated peptide cleavage. PMID: 19883612 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963487 Sun, 01 Nov 2009 00:00:00 +0100 2963487 http://www.medworm.com/index.php?rid=2963486&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%3D19883613%26dopt%3DAbstract Authors: Al-Qassab H, Smith MA, Irvine EE, Guillermet-Guibert J, Claret M, Choudhury AI, Selman C, Piipari K, Clements M, Lingard S, Chandarana K, Bell JD, Barsh GS, Smith AJ, Batterham RL, Ashford ML, Vanhaesebroeck B, Withers DJ PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through largely unknown mechanisms. We inactivated either p110alpha or p110beta PI3K catalytic subunits in these neurons and demonstrate a dominant role for the latter in energy homeostasis regulation. In POMC neurons, p110beta inactivation prevented insulin- and leptin-stimulated electrophysiological responses. POMCp110beta null mice exhibited central leptin resistance, inc... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963486 Sun, 01 Nov 2009 00:00:00 +0100 2963486 http://www.medworm.com/index.php?rid=2963485&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%3D19883614%26dopt%3DAbstract Authors: Maejima Y, Sedbazar U, Suyama S, Kohno D, Onaka T, Takano E, Yoshida N, Koike M, Uchiyama Y, Fujiwara K, Yashiro T, Horvath TL, Dietrich MO, Tanaka S, Dezaki K, Oh-I S, Hashimoto K, Shimizu H, Nakata M, Mori M, Yada T The hypothalamic paraventricular nucleus (PVN) functions as a center to integrate various neuronal activities for regulating feeding behavior. Nesfatin-1, a recently discovered anorectic molecule, is localized in the PVN. However, the anorectic neural pathway of nesfatin-1 remains unknown. Here we show that central injection of nesfatin-1 activates the PVN and brain stem nucleus tractus solitarius (NTS). In the PVN, nesfatin-1 targets both magnocellular and parvocellular oxytocin neurons and nesfatin-1 neurons themselves and stimulates oxytocin release. Immunoele... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963485 Sun, 01 Nov 2009 00:00:00 +0100 2963485 http://www.medworm.com/index.php?rid=2963484&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%3D19883615%26dopt%3DAbstract Authors: Costanzo-Garvey DL, Pfluger PT, Dougherty MK, Stock JL, Boehm M, Chaika O, Fernandez MR, Fisher K, Kortum RL, Hong EG, Jun JY, Ko HJ, Schreiner A, Volle DJ, Treece T, Swift AL, Winer M, Chen D, Wu M, Leon LR, Shaw AS, McNeish J, Kim JK, Morrison DK, Tschöp MH, Lewis RE Kinase suppressors of Ras 1 and 2 (KSR1 and KSR2) function as molecular scaffolds to potently regulate the MAP kinases ERK1/2 and affect multiple cell fates. Here we show that KSR2 interacts with and modulates the activity of AMPK. KSR2 regulates AMPK-dependent glucose uptake and fatty acid oxidation in mouse embryonic fibroblasts and glycolysis in a neuronal cell line. Disruption of KSR2 in vivo impairs AMPK-regulated processes affecting fatty acid oxidation and thermogenesis to cause obesity. Despite thei... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963484 Sun, 01 Nov 2009 00:00:00 +0100 2963484 http://www.medworm.com/index.php?rid=2963483&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%3D19883616%26dopt%3DAbstract Authors: Lee SJ, Murphy CT, Kenyon C Many studies have addressed the effect of dietary glycemic index on obesity and diabetes, but little is known about its effect on life span itself. We found that adding a small amount of glucose to the medium (2%) shortened the life span of C. elegans by inhibiting the activities of life span-extending transcription factors that are also inhibited by insulin signaling: the FOXO family member DAF-16 and the heat shock factor HSF-1. This effect involved the downregulation of an aquaporin glycerol channel, aqp-1. We show that changes in glycerol metabolism are likely to underlie the life span-shortening effect of glucose and that aqp-1 may act cell nonautonomously as a feedback regulator in the insulin/IGF-1-signaling pathway. Insulin downregulates sim... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963483 Sun, 01 Nov 2009 00:00:00 +0100 2963483 http://www.medworm.com/index.php?rid=2963482&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%3D19883617%26dopt%3DAbstract Authors: Kemper JK, Xiao Z, Ponugoti B, Miao J, Fang S, Kanamaluru D, Tsang S, Wu SY, Chiang CM, Veenstra TD The nuclear bile acid receptor FXR is critical for regulation of lipid and glucose metabolism. Here, we report that FXR is a target of SIRT1, a deacetylase that mediates nutritional and hormonal modulation of hepatic metabolism. Lysine 217 of FXR is the major acetylation site targeted by p300 and SIRT1. Acetylation of FXR increases its stability but inhibits heterodimerization with RXRalpha, DNA binding, and transactivation activity. Downregulation of hepatic SIRT1 increased FXR acetylation with deleterious metabolic outcomes. Surprisingly, in mouse models of metabolic disease, FXR interaction with SIRT1 and p300 was dramatically altered, FXR acetylation levels were elevated, an... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963482 Sun, 01 Nov 2009 00:00:00 +0100 2963482 http://www.medworm.com/index.php?rid=2963481&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%3D19883618%26dopt%3DAbstract Authors: Leavens KF, Easton RM, Shulman GI, Previs SF, Birnbaum MJ Insulin drives the global anabolic response to nutrient ingestion, regulating both carbohydrate and lipid metabolism. Previous studies have demonstrated that Akt2/protein kinase B is critical to insulin's control of glucose metabolism, but its role in lipid metabolism has remained controversial. Here, we show that Akt2 is required for hepatic lipid accumulation in obese, insulin-resistant states induced by either leptin deficiency or high-fat diet feeding. Lep(ob/ob) mice lacking hepatic Akt2 failed to amass triglycerides in their livers, associated with and most likely due to a decrease in lipogenic gene expression and de novo lipogenesis. However, Akt2 is also required for steatotic pathways unrelated to fatty acid sy... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963481 Sun, 01 Nov 2009 00:00:00 +0100 2963481 http://www.medworm.com/index.php?rid=2963480&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%3D19883619%26dopt%3DAbstract Authors: Saberi M, Woods NB, de Luca C, Schenk S, Lu JC, Bandyopadhyay G, Verma IM, Olefsky JM Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4(-/-)) and control (BMT-WT) mice. After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4(-/-) mice became obese but did not develop fasting hyperinsulinemia and had... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963480 Sun, 01 Nov 2009 00:00:00 +0100 2963480 http://www.medworm.com/index.php?rid=2963479&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%3D19883620%26dopt%3DAbstract Authors: O'Rourke EJ, Soukas AA, Carr CE, Ruvkun G Genetic conservation allows ancient features of fat storage endocrine pathways to be explored in C. elegans. Multiple studies have used Nile red or BODIPY-labeled fatty acids to identify regulators of fat mass. When mixed with their food, E. coli bacteria, Nile red, and BODIPY-labeled fatty acids stain multiple spherical cellular structures in the C. elegans major fat storage organ, the intestine. However, here we demonstrate that, in the conditions previously reported, the lysosome-related organelles stained by Nile red and BODIPY-labeled fatty acids are not the C. elegans major fat storage compartment. We show that the major fat stores are contained in a distinct cellular compartment that is not stained by Nile red. Using biochemical... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2963479 Sun, 01 Nov 2009 00:00:00 +0100 2963479 http://www.medworm.com/index.php?rid=2872670&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%3D19808014%26dopt%3DAbstract Authors: Wisse BE, Schwartz MW Obesity-induced inflammation causes cellular resistance to both insulin and leptin. In this issue, Brüning and colleagues (Kleinridders et al., 2009) add to growing evidence that this response occurs in the hypothalamus, as well as in peripheral tissues, which helps to explain how high-fat feeding induces a gradual increase in defended body weight. PMID: 19808014 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872670 Wed, 30 Sep 2009 23:00:00 +0100 2872670 http://www.medworm.com/index.php?rid=2872669&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%3D19808015%26dopt%3DAbstract Authors: Rosen CJ In a paper by Yadav and colleagues, a novel pathway linking the central nervous system effects of leptin on bone mass and energy expenditure to serotonin signaling in brainstem circuits is described. The data from those studies strengthen the tenet that skeletal remodeling is intimately connected to central regulation of metabolism. PMID: 19808015 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872669 Wed, 30 Sep 2009 23:00:00 +0100 2872669 http://www.medworm.com/index.php?rid=2872668&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%3D19808016%26dopt%3DAbstract Authors: De Domenico I, Kaplan J The unfolded protein response (UPR) coordinates translational and transcriptional changes triggered by unfolded proteins within the endoplasmic reticulum. Two recent papers (Oliveira et al., 2009; Vecchi et al., 2009) show that the UPR modulates transcription of the hormone hepcidin, which controls plasma iron levels and perhaps innate immunity. PMID: 19808016 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872668 Wed, 30 Sep 2009 23:00:00 +0100 2872668 http://www.medworm.com/index.php?rid=2872667&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%3D19808017%26dopt%3DAbstract Authors: Kennedy BK, Mackay VL Several studies indicate that reduced TOR signaling underlies life span extension by dietary restriction. Recently, Zid et al. (Zid et al., 2009) linked the benefits of dietary restriction in flies to increased levels of the downstream TOR target 4E-BP1 and corresponding changes in the relative translation rates of classes of mRNAs. PMID: 19808017 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872667 Wed, 30 Sep 2009 23:00:00 +0100 2872667 http://www.medworm.com/index.php?rid=2872666&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%3D19808018%26dopt%3DAbstract Authors: Kleinridders A, Schenten D, Könner AC, Belgardt BF, Mauer J, Okamura T, Wunderlich FT, Medzhitov R, Brüning JC Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR4 signaling by fatty acids. Here, we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterized mice deficient for the TLR adaptor molecule MyD88 in the CNS (MyD88(DeltaCNS)). Compared to control mice, MyD88(DeltaCNS) mice are protected from high-fat diet (HFD)-in... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872666 Wed, 30 Sep 2009 23:00:00 +0100 2872666 http://www.medworm.com/index.php?rid=2872665&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%3D19808019%26dopt%3DAbstract Authors: Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S, Bruce C, Shields BJ, Skiba B, Ooms LM, Stepto N, Wu B, Mitchell CA, Tonks NK, Watt MJ, Febbraio MA, Crack PJ, Andrikopoulos S, Tiganis T Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high-fat-diet-induced insulin resistance. The increased in... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872665 Wed, 30 Sep 2009 23:00:00 +0100 2872665 http://www.medworm.com/index.php?rid=2872664&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%3D19808020%26dopt%3DAbstract Authors: Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, Loscalzo J Repression of mitochondrial respiration represents an evolutionarily ancient cellular adaptation to hypoxia and profoundly influences cell survival and function; however, the underlying molecular mechanisms are incompletely understood. Primarily utilizing pulmonary arterial endothelial cells as a representative hypoxic cell type, we identify the iron-sulfur cluster assembly proteins (ISCU1/2) as direct targets for repression by the hypoxia-induced microRNA-210 (miR-210). ISCU1/2 facilitate the assembly of iron-sulfur clusters, prosthetic groups that are critical for electron transport and mitochondrial oxidation-reduction reactions. Under in vivo conditions of upregulating miR-210 and repressing ISCU1/2, the integr... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872664 Wed, 30 Sep 2009 23:00:00 +0100 2872664 http://www.medworm.com/index.php?rid=2872663&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%3D19808021%26dopt%3DAbstract Authors: Fu A, Ng AC, Depatie C, Wijesekara N, He Y, Wang GS, Bardeesy N, Scott FW, Touyz RM, Wheeler MB, Screaton RA The Lkb1 tumor suppressor exerts its biological effects through phosphorylation and consequent activation of the AMP kinase (AMPK) family. Extensive genetic and biochemical evidence supports a role for Lkb1 in cell cycle arrest, establishment of cell polarity, and cellular energy metabolism. However, the role of Lkb1 and the AMPK family in beta cell function in vivo has not been established. We generated conditional knockout mice with a deletion of the Lkb1 gene in the beta cell compartment of pancreatic islets; these mice display improved glucose tolerance and protection against diet-induced hyperglycemia. Lkb1(-/-) beta cells are hypertrophic because of elevated mTOR ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872663 Wed, 30 Sep 2009 23:00:00 +0100 2872663 http://www.medworm.com/index.php?rid=2872662&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%3D19808022%26dopt%3DAbstract Authors: Granot Z, Swisa A, Magenheim J, Stolovich-Rain M, Fujimoto W, Manduchi E, Miki T, Lennerz JK, Stoeckert CJ, Meyuhas O, Seino S, Permutt MA, Piwnica-Worms H, Bardeesy N, Dor Y Pancreatic beta cells, organized in the islets of Langerhans, sense glucose and secrete appropriate amounts of insulin. We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult beta cells. LKB1-deficient beta cells show a dramatic increase in insulin secretion in vivo. Histologically, LKB1-deficient beta cells have striking alterations in the localization of the nucleus and cilia relative to blood vessels, suggesting a shift from hepatocyte-like to columnar polarity. Additionally, LKB1 deficiency causes a 65% increase in beta cell vol... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872662 Wed, 30 Sep 2009 23:00:00 +0100 2872662 http://www.medworm.com/index.php?rid=2872661&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%3D19808023%26dopt%3DAbstract Authors: Li DQ, Jing X, Salehi A, Collins SC, Hoppa MB, Rosengren AH, Zhang E, Lundquist I, Olofsson CS, Mörgelin M, Eliasson L, Rorsman P, Renström E Priming of insulin secretory granules for release requires intragranular acidification and depends on vesicular Cl(-)-fluxes, but the identity of the chloride transporter/ion channel involved is unknown. We tested the hypothesis that the chloride transport protein ClC-3 fulfills these actions in pancreatic beta cells. In ClC-3(-/-) mice, insulin secretion evoked by membrane depolarization (high extracellular K(+), sulfonylureas), or glucose was >60% reduced compared to WT animals. This effect was mirrored by a approximately 80% reduction in depolarization-evoked beta cell exocytosis (monitored as increases in cell capacitanc... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872661 Wed, 30 Sep 2009 23:00:00 +0100 2872661 http://www.medworm.com/index.php?rid=2872660&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%3D19808024%26dopt%3DAbstract In this study, immuno-EM of beta cells revealed colocalization of ClC-3 and insulin on secretory granules. Clcn3(-/-) mice as well as isolated islets demonstrate impaired insulin secretion; Clcn3(-/-) beta cells are defective in regulated insulin exocytosis and granular acidification. Increased amounts of proinsulin were found in the majority of secretory granules in the Clcn3(-/-) mice, while in Clcn3(+/+) cells, proinsulin was confined to the immature secretory granules. These results demonstrate that in pancreatic beta cells, chloride channels, specifically ClC-3, are localized on insulin granules and play a role in insulin processing as well as insulin secretion through regulation of granular acidification. PMID: 19808024 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872660 Wed, 30 Sep 2009 23:00:00 +0100 2872660 http://www.medworm.com/index.php?rid=2872659&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%3D19808025%26dopt%3DAbstract Authors: Forner F, Kumar C, Luber CA, Fromme T, Klingenspor M, Mann M Mitochondria are functionally specialized in different tissues, and a detailed understanding of this specialization is important to elucidate mitochondrial involvement in normal physiology and disease. In adaptive thermogenesis, brown fat converts mitochondrial energy to heat, whereas tissue-specific functions of mitochondria in white fat are less characterized. Here we apply high-resolution quantitative mass spectrometry to directly and accurately compare the in vivo mouse mitochondrial proteomes of brown and white adipocytes. Their proteomes are substantially different qualitatively and quantitatively and are furthermore characterized by tissue-specific protein isoforms, which are modulated by cold exposure. At tra... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2872659 Wed, 30 Sep 2009 23:00:00 +0100 2872659 http://www.medworm.com/index.php?rid=2762382&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%3D19723490%26dopt%3DAbstract Authors: Ory DS Lipoprotein cholesterol is mobilized from lysosomes by actions of the NPC1 and NPC2 proteins. In this issue of Cell Metabolism, Harrison et al. report on identification of an NPC2-interacting protein, the Nogo-B receptor, that regulates NPC2 protein levels. NPC2 stabilization may represent a novel mechanism through which cells respond to endocytosed cholesterol. PMID: 19723490 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762382 Mon, 31 Aug 2009 23:00:00 +0100 2762382 http://www.medworm.com/index.php?rid=2762381&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%3D19723491%26dopt%3DAbstract Authors: Vallim TQ, Edwards PA In this issue of Cell Metabolism, Thomas et al. (2009) show that specific activation of the bile-acid-activated G protein-coupled receptor TGR5 improves pancreatic and hepatic function and impairs the development of obesity following administration of a high-fat diet. PMID: 19723491 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762381 Mon, 31 Aug 2009 23:00:00 +0100 2762381 http://www.medworm.com/index.php?rid=2762380&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%3D19723492%26dopt%3DAbstract Authors: Tatar M Drosophila melanogaster produce insulin-like peptides in specialized neuroendocrine cells to regulate growth, metabolism, aging, and reproduction. In this issue of Cell Metabolism, Géminard et al. (2009) describe how secretion of insulin-like peptides is remotely controlled by the fat body (an adipose, liver-like tissue) in response to dietary amino acids. PMID: 19723492 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762380 Mon, 31 Aug 2009 23:00:00 +0100 2762380 http://www.medworm.com/index.php?rid=2762379&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%3D19723493%26dopt%3DAbstract Authors: Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies in vivo, we show here that TGR5 signaling induces intestinal glucagon-like peptide-1 (GLP-1) release, leading to improved liver and pancreatic function and enhanced glucose tolerance in obese mice. In addition, we show that the induction of GLP-1 release in enteroendocrine cells by 6alpha-ethyl-23(S)-methyl-cholic acid (EMCA, INT-777), a specific TGR5 ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762379 Mon, 31 Aug 2009 23:00:00 +0100 2762379 http://www.medworm.com/index.php?rid=2762378&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%3D19723494%26dopt%3DAbstract Authors: Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, Urano T, Zhu HJ, Tsukano H, Tazume H, Kaikita K, Miyashita K, Iwawaki T, Shimabukuro M, Sakaguchi K, Ito T, Nakagata N, Yamada T, Katagiri H, Kasuga M, Ando Y, Ogawa H, Mochizuki N, Itoh H, Suda T, Oike Y Recent studies of obesity have provided new insights into the mechanisms underlying insulin resistance and metabolic dysregulation. Numerous efforts have been made to identify key regulators of obesity-linked adipose tissue inflammation and insulin resistance. We found that angiopoietin-like protein 2 (Angptl2) was secreted by adipose tissue and that its circulating level was closely related to adiposity, systemic insulin resistance, and inflammation in both mice and humans. Angptl2 activated an inflammatory cascade ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762378 Mon, 31 Aug 2009 23:00:00 +0100 2762378 http://www.medworm.com/index.php?rid=2762377&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%3D19723495%26dopt%3DAbstract Authors: Barrès R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, Zierath JR Epigenetic modification through DNA methylation is implicated in metabolic disease. Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) in diabetic subjects. Methylation levels were negatively correlated with PGC-1alpha mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1alpha was found within non-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alph... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762377 Mon, 31 Aug 2009 23:00:00 +0100 2762377 http://www.medworm.com/index.php?rid=2762376&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%3D19723496%26dopt%3DAbstract Authors: Géminard C, Rulifson EJ, Léopold P Insulin-like peptides (ILPs) couple growth, metabolism, longevity, and fertility with changes in nutritional availability. In Drosophila, several ILPs called Dilps are produced by the brain insulin-producing cells (IPCs), from which they are released into the hemolymph and act systemically. We show here that in response to nutrient deprivation, brain Dilps are no longer secreted and accumulate in the IPCs. We further demonstrate that the larval fat body, a functional homolog of vertebrate liver and white fat, couples the level of circulating Dilps with dietary amino acid levels by remotely controlling Dilp release through a TOR/RAPTOR-dependent mechanism. We finally use ex vivo tissue coculture to demonstrate that a humoral signal e... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762376 Mon, 31 Aug 2009 23:00:00 +0100 2762376 http://www.medworm.com/index.php?rid=2762375&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%3D19723497%26dopt%3DAbstract Authors: Harrison KD, Miao RQ, Fernandez-Hernándo C, Suárez Y, Dávalos A, Sessa WC The Nogo-B receptor (NgBR) is a recently identified receptor for the N terminus of reticulon 4B/Nogo-B. Other than its role in binding Nogo-B, little is known about the biology of NgBR. To elucidate a basic cellular role for NgBR, we performed a yeast two-hybrid screen for interacting proteins, using the C-terminal domain as bait, and identified Niemann-Pick type C2 protein (NPC2) as an NgBR-interacting protein. NPC2 protein levels are increased in the presence of NgBR, and NgBR enhances NPC2 protein stability. NgBR localizes primarily to the endoplasmic reticulum (ER) and regulates the stability of nascent NPC2. RNAi-mediated disruption of NgBR or genetic deficiency in NgBR lead to a decr... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762375 Mon, 31 Aug 2009 23:00:00 +0100 2762375 http://www.medworm.com/index.php?rid=2762374&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%3D19723498%26dopt%3DAbstract Authors: Sekiya M, Osuga J, Nagashima S, Ohshiro T, Igarashi M, Okazaki H, Takahashi M, Tazoe F, Wada T, Ohta K, Takanashi M, Kumagai M, Nishi M, Takase S, Yahagi N, Yagyu H, Ohashi K, Nagai R, Kadowaki T, Furukawa Y, Ishibashi S Cholesterol ester (CE)-laden macrophage foam cells are the hallmark of atherosclerosis, and the hydrolysis of intracellular CE is one of the key steps in foam cell formation. Although hormone-sensitive lipase (LIPE) and cholesterol ester hydrolase (CEH), which is identical to carboxylsterase 1 (CES1, hCE1), were proposed to mediate the neutral CE hydrolase (nCEH) activity in macrophages, recent evidences have suggested the involvement of other enzymes. We have recently reported the identification of a candidate, neutral cholesterol ester hydrolase 1(Nceh1). He... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762374 Mon, 31 Aug 2009 23:00:00 +0100 2762374 http://www.medworm.com/index.php?rid=2762373&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%3D19723499%26dopt%3DAbstract Authors: Terauchi M, Li JY, Bedi B, Baek KH, Tawfeek H, Galley S, Gilbert L, Nanes MS, Zayzafoon M, Guldberg R, Lamar DL, Singer MA, Lane TF, Kronenberg HM, Weitzmann MN, Pacifici R Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anaboli... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2762373 Mon, 31 Aug 2009 23:00:00 +0100 2762373 http://www.medworm.com/index.php?rid=2682666&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%3D19656482%26dopt%3DAbstract Authors: DiLeone RJ The metabolic hormone leptin influences feeding and metabolism through action on a distributed brain network. In this issue, Leinninger et al. (2009) describe a novel lateral hypothalamic neuronal population that is responsive to leptin and interfaces with dopamine circuits. PMID: 19656482 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682666 Fri, 31 Jul 2009 23:00:00 +0100 2682666 http://www.medworm.com/index.php?rid=2682665&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%3D19656483%26dopt%3DAbstract Authors: Jones DL Germ cells possess the unique ability to transmit genetic information from generation to generation. In a recent paper, Curran et al. (2009) explore the possibility that some features of germ cells, including enhanced genomic stability, can be acquired by the soma as a mechanism to increase longevity. PMID: 19656483 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682665 Fri, 31 Jul 2009 23:00:00 +0100 2682665 http://www.medworm.com/index.php?rid=2682664&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%3D19656484%26dopt%3DAbstract Authors: Rouault TA, Tong WH A large-scale computational and genetic analysis study by Nilsson et al. (2009) has identified five genes that coexpress with heme biosynthetic enzymes and are required for normal heme synthesis. Several are implicated in iron-sulfur cluster biogenesis, and malfunction of these genes may repress heme synthesis by activating the IRE/IRP posttranscriptional regulatory system. PMID: 19656484 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682664 Fri, 31 Jul 2009 23:00:00 +0100 2682664 http://www.medworm.com/index.php?rid=2682663&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%3D19656485%26dopt%3DAbstract Authors: Smith RG The octanoylated peptide hormone ghrelin regulates episodic growth hormone release and energy balance. Work in genetically modified mice (Kirchner et al., 2009) now shows that in vivo activity of ghrelin O-acyltransferase (GOAT), responsible for ghrelin octanoylation, decreases during fasting but increases after ingesting medium-chain fatty acid triglycerides (MCT). PMID: 19656485 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682663 Fri, 31 Jul 2009 23:00:00 +0100 2682663 http://www.medworm.com/index.php?rid=2682662&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%3D19656486%26dopt%3DAbstract Authors: Simpson RJ, McKie AT Two studies (Shah et al., 2009; Mastrogiannaki et al., 2009) show that the hypoxia inducible factor HIF-2alpha is a major player in regulating iron absorption by directly controlling the transcription of iron transporters in the intestine in response to changes in mucosal iron or oxygen levels. The HIF-2alpha mechanism has major effects on iron metabolism which can override the well-known hepcidin-ferroportin regulatory axis. PMID: 19656486 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682662 Fri, 31 Jul 2009 23:00:00 +0100 2682662 http://www.medworm.com/index.php?rid=2682661&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%3D19656487%26dopt%3DAbstract Authors: Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, Wilson H, Opland DM, Faouzi MA, Gong Y, Jones JC, Rhodes CJ, Chua S, Diano S, Horvath TL, Seeley RJ, Becker JB, Münzberg H, Myers MG The lateral hypothalamic area (LHA) acts in concert with the ventral tegmental area (VTA) and other components of the mesolimbic dopamine (DA) system to control motivation, including the incentive to feed. The anorexigenic hormone leptin modulates the mesolimbic DA system, although the mechanisms underlying this control have remained incompletely understood. We show that leptin directly regulates a population of leptin receptor (LepRb)-expressing inhibitory neurons in the LHA and that leptin action via these LHA LepRb neurons decreases feeding and body weight. Furthermore, these ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682661 Fri, 31 Jul 2009 23:00:00 +0100 2682661 http://www.medworm.com/index.php?rid=2682660&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%3D19656488%26dopt%3DAbstract Authors: Cheung GW, Kokorovic A, Lam CK, Chari M, Lam TK Cholecystokinin (CCK) is a peptide hormone that is released from the gut in response to nutrients such as lipids to lower food intake. Here we report that a primary increase of CCK-8, the biologically active form of CCK, in the duodenum lowers glucose production independent of changes in circulating insulin levels. Furthermore, we show that duodenal CCK-8 requires the activation of the gut CCK-A receptor and a gut-brain-liver neuronal axis to lower glucose production. Finally, duodenal CCK-8 fails to lower glucose production in the early onset of high-fat diet-induced insulin resistance. These findings reveal a role for gut CCK that lowers glucose production through a neuronal network and suggest that intestinal CCK resistance ma... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682660 Fri, 31 Jul 2009 23:00:00 +0100 2682660 http://www.medworm.com/index.php?rid=2682659&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%3D19656489%26dopt%3DAbstract Authors: Gauthier BR, Wiederkehr A, Baquié M, Dai C, Powers AC, Kerr-Conte J, Pattou F, MacDonald RJ, Ferrer J, Wollheim CB Mutations in the transcription factor Pdx1 cause maturity-onset diabetes of the young 4 (MODY4). Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). Transcript profiling revealed suppression of nuclear-encoded mitochondrial factor A (TFAM). Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia. We define TFAM as a direct target of Pdx1 both in rat INS1 cells and human islets. Adenoviral overexpression of TFAM along with RIPDN79PDX1 in isolated rat islets rescued mitochondrial DNA (mtDNA) copy number and restored ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682659 Fri, 31 Jul 2009 23:00:00 +0100 2682659 http://www.medworm.com/index.php?rid=2682657&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%3D19656490%26dopt%3DAbstract Authors: Nilsson R, Schultz IJ, Pierce EL, Soltis KA, Naranuntarat A, Ward DM, Baughman JM, Paradkar PN, Kingsley PD, Culotta VC, Kaplan J, Palis J, Paw BH, Mootha VK Heme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional mitochondrial transporters and regulatory factors are predicted to be required. To discover such unknown components, we utilized a large-scale computational screen to identify mitochondrial proteins whose transcripts consistently coexpress with the core machinery of heme biosynthesis. We identified SLC25A39, SLC22A4, and TMEM14C, which are putative mitochondrial transporters, as well as C1orf69 and ISCA1, wh... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682657 Fri, 31 Jul 2009 23:00:00 +0100 2682657 http://www.medworm.com/index.php?rid=2682654&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%3D19656491%26dopt%3DAbstract We report that mitochondrial protein synthesis is unimpaired in mtDNA mutator mice consistent with the observed minor alterations of steady-state levels of mitochondrial transcripts. These findings refute recent claims that circular mtDNA molecules with large deletions are driving the premature aging phenotype. We further show that the stability of several respiratory chain complexes is severely impaired despite normal synthesis of the corresponding mtDNA-encoded subunits. Our findings reveal a mechanism for induction of aging phenotypes by demonstrating a causative role for amino acid substitutions in mtDNA-encoded respiratory chain subunits, which, in turn, leads to decreased stability of the respiratory chain complexes and respiratory chain deficiency. PMID: 19656491 [PubMed - in pr... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682654 Fri, 31 Jul 2009 23:00:00 +0100 2682654 http://www.medworm.com/index.php?rid=2682653&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%3D19656492%26dopt%3DAbstract Authors: Idris AI, Sophocleous A, Landao-Bassonga E, Canals M, Milligan G, Baker D, van't Hof RJ, Ralston SH Age-related osteoporosis is characterized by reduced bone formation and accumulation of fat in the bone marrow compartment. Here, we report that the type 1 cannabinoid receptor (CB1) regulates this process. Mice with CB1 deficiency (CB1(-/-)) had increased peak bone mass due to reduced bone resorption, but developed age-related osteoporosis with reduced bone formation and accumulation of adipocytes in the bone marrow space. Marrow stromal cells from CB1(-/-) mice had an enhanced capacity for adipocyte differentiation, a reduced capacity for osteoblast differentiation, and increased expression of phosphorylated CREB (pCREB) and PPARgamma. Pharmacological blockade of CB1 receptors... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682653 Fri, 31 Jul 2009 23:00:00 +0100 2682653 http://www.medworm.com/index.php?rid=2682652&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%3D19656493%26dopt%3DAbstract Authors: Ceccarini G, Flavell RR, Butelman ER, Synan M, Willnow TE, Bar-Dagan M, Goldsmith SJ, Kreek MJ, Kothari P, Vallabhajosula S, Muir TW, Friedman JM We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using (18)F- and (68)Ga-labeled leptin revealed that, in mouse, the hormone was rapidly taken up by megalin (gp330/LRP2), a multiligand endocytic receptor localized in renal tubules. In addition, in rhesus monkeys, 15% of labeled leptin localized to red bone marrow, which was consistent with hormone uptake in rodent tissues. These data confirm a megalin-dependent mechanism for renal uptake in vivo. The significant binding to immune cells and blood cell precursors in bone marrow is also consistent with prior evidence showing that leptin m... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2682652 Fri, 31 Jul 2009 23:00:00 +0100 2682652 http://www.medworm.com/index.php?rid=2588675&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%3D19583945%26dopt%3DAbstract Authors: Wek RC, Anthony TG In this issue of Cell Metabolism, Kaufman and colleagues (Back et al., 2009) elegantly demonstrate that appropriate regulation of eIF2alpha phosphorylation improves glucose tolerance and beta cell viability by preventing the lethal buildup of oxidative damage due to unregulated synthesis, trafficking, and misfolding of proteins. PMID: 19583945 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588675 Tue, 30 Jun 2009 23:00:00 +0100 2588675 http://www.medworm.com/index.php?rid=2588674&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%3D19583946%26dopt%3DAbstract Authors: Munkacsi AB, Pentchev PG, Sturley SL Endocytosed cholesterol must be transferred from the environment (e.g., low-density lipoproteins) via the lysosomal system to the rest of the cell. In Niemann-Pick type C disease, this process fails. In a recent issue of Cell, Kwon et al. (2009) suggest how this transpires mechanistically by crystallizing a domain of a protein defective in this syndrome. PMID: 19583946 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588674 Tue, 30 Jun 2009 23:00:00 +0100 2588674 http://www.medworm.com/index.php?rid=2588673&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%3D19583947%26dopt%3DAbstract Authors: Young LH AMP-activated protein kinase (AMPK) is a key metabolic regulator. Recent work (Chen et al., 2009) elucidates the structural interaction between the autoinhibitory sequence and the kinase domain of the AMPK catalytic subunit. Enhanced understanding of the molecular mechanics of AMPK activation might lead to novel therapeutic approaches. PMID: 19583947 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588673 Tue, 30 Jun 2009 23:00:00 +0100 2588673 http://www.medworm.com/index.php?rid=2588672&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%3D19583948%26dopt%3DAbstract Authors: Ferron M, Karsenty G Though surgical removal of the stomach has long been linked to low bone mass, the molecular mechanism has been elusive. Amling and coworkers now demonstrate that gastric cell acid production is necessary for calcium absorption. Mice lacking this acidification develop hypocalcemia, with increased parathyroid hormone and osteoclast differentiation, and decreased bone mass. PMID: 19583948 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588672 Tue, 30 Jun 2009 23:00:00 +0100 2588672 http://www.medworm.com/index.php?rid=2588671&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%3D19583949%26dopt%3DAbstract Authors: Brookheart RT, Michel CI, Schaffer JE Excess fatty acid accumulation in nonadipose tissues is a hallmark of metabolic disease. When elevated lipid levels exceed the cell's capacity to store or utilize fatty acids, a lipotoxic-response is elicited, characterized by destruction of organelle membranes, activation of stress pathways, and apoptosis. This Minireview focuses on the mechanisms by which lipid overload causes nonadipose cell death and contributes to the pathogenesis of obesity and diabetes. PMID: 19583949 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588671 Tue, 30 Jun 2009 23:00:00 +0100 2588671 http://www.medworm.com/index.php?rid=2588670&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%3D19583950%26dopt%3DAbstract Authors: Back SH, Scheuner D, Han J, Song B, Ribick M, Wang J, Gildersleeve RD, Pennathur S, Kaufman RJ Accumulation of unfolded protein within the endoplasmic reticulum (ER) attenuates mRNA translation through PERK-mediated phosphorylation of eukaryotic initiation factor 2 on Ser51 of the alpha subunit (eIF2alpha). To elucidate the role of eIF2alpha phosphorylation, we engineered mice for conditional expression of homozygous Ser51Ala mutant eIF2alpha. The absence of eIF2alpha phosphorylation in beta cells caused a severe diabetic phenotype due to heightened and unregulated proinsulin translation; defective intracellular trafficking of ER cargo proteins; increased oxidative damage; reduced expression of stress response and beta-cell-specific genes; and apoptosis. However, glucose intol... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588670 Tue, 30 Jun 2009 23:00:00 +0100 2588670 http://www.medworm.com/index.php?rid=2588669&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%3D19583951%26dopt%3DAbstract Authors: Cho YW, Hong S, Jin Q, Wang L, Lee JE, Gavrilova O, Ge K PPARgamma and C/EBPalpha cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARgamma and C/EBPalpha expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARgamma and C/EBPalpha expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARgamma expression and PPARgamma-stimulated C/EBPalpha expression. Further, PTIP is essential for induction of PPARgamma and C/EBPalpha expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymer... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588669 Tue, 30 Jun 2009 23:00:00 +0100 2588669 http://www.medworm.com/index.php?rid=2588668&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%3D19583952%26dopt%3DAbstract Authors: Crowe S, Wu LE, Economou C, Turpin SM, Matzaris M, Hoehn KL, Hevener AL, James DE, Duh EJ, Watt MJ Obesity is a major risk factor for insulin resistance; however, the factors linking these disorders are not well defined. Herein, we show that the noninhibitory serine protease inhibitor, pigment epithelium-derived factor (PEDF), plays a causal role in insulin resistance. Adipocyte PEDF expression and serum levels are elevated in several rodent models of obesity and reduced upon weight loss and insulin sensitization. Lean mice injected with recombinant PEDF exhibited reduced insulin sensitivity during hyperinsulinemic-euglycemic clamps. Acute PEDF administration activated the proinflammatory serine/threonine kinases c-Jun terminal kinase and extracellular regulated kinase in both... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588668 Tue, 30 Jun 2009 23:00:00 +0100 2588668 http://www.medworm.com/index.php?rid=2588667&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%3D19583953%26dopt%3DAbstract Authors: Fernández-Hernando C, Yu J, Suárez Y, Rahner C, Dávalos A, Lasunción MA, Sessa WC The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588667 Tue, 30 Jun 2009 23:00:00 +0100 2588667 http://www.medworm.com/index.php?rid=2588666&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%3D19583954%26dopt%3DAbstract Authors: Le Lay J, Tuteja G, White P, Dhir R, Ahima R, Kaestner KH The liver contributes to glucose homeostasis by promoting either storage or production of glucose, depending on the physiological state. The cAMP response element-binding protein (CREB) is a principal regulator of genes involved in coordinating the hepatic response to fasting, but its mechanism of gene activation remains controversial. We derived CRTC2 (CREB-regulated transcription coactivator 2, previously TORC2)-deficient mice to assess the contribution of this cofactor to hepatic glucose metabolism in vivo. CRTC2 mutant hepatocytes showed reduced glucose production in response to glucagon, which correlated with decreased CREB binding to several gluconeogenic genes. However, despite attenuated expression of CREB targe... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588666 Tue, 30 Jun 2009 23:00:00 +0100 2588666 http://www.medworm.com/index.php?rid=2588665&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%3D19583955%26dopt%3DAbstract Authors: Bartz F, Kern L, Erz D, Zhu M, Gilbert D, Meinhof T, Wirkner U, Erfle H, Muckenthaler M, Pepperkok R, Runz H Elevated plasma cholesterol levels are considered responsible for excess cardiovascular morbidity and mortality. Cholesterol in plasma is tightly controlled by cholesterol within cells. Here, we developed and applied an integrative functional genomics strategy that allows systematic identification of regulators of cellular cholesterol levels. Candidate genes were identified by genome-wide gene-expression profiling of sterol-depleted cells and systematic literature queries. The role of these genes in cholesterol regulation was then tested by targeted siRNA knockdown experiments quantifying cellular cholesterol levels and the efficiency of low-density lipoprotein (LDL) up... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2588665 Tue, 30 Jun 2009 23:00:00 +0100 2588665 http://www.medworm.com/index.php?rid=2527147&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%3D19490901%26dopt%3DAbstract Authors: Pei L, Evans RM In this issue of Cell Metabolism, Liao and colleagues have applied a novel synthetic approach to fight obesity in animals by engineering the plant glyoxylate shunt in vivo (Dean et al., 2009). The idea of introducing an entirely foreign metabolic pathway opens up opportunities for understanding metabolism and creating novel potential therapeutic approaches. PMID: 19490901 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527147 Sun, 31 May 2009 23:00:00 +0100 2527147 http://www.medworm.com/index.php?rid=2527145&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%3D19490902%26dopt%3DAbstract Authors: White MF A recent Cell paper by He et al. (2009) shows how metformin circumvents a block between insulin and atypical protein kinase C in obese and diabetic mice to inhibit gluconeogenesis by stimulating the phosphorylation of CBP and the disassembly of the CREB transcriptional complex. PMID: 19490902 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527145 Sun, 31 May 2009 23:00:00 +0100 2527145 http://www.medworm.com/index.php?rid=2527143&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%3D19490903%26dopt%3DAbstract Authors: Farooqi S Maternal inheritance of mutations in the GNAS1 gene is associated with obesity in humans, but the mechanism involved is unknown. In this issue, Chen et al. (2009) have generated mice with brain specific deletion of either the maternal or paternal allele to trace the origin of the phenotype. PMID: 19490903 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527143 Sun, 31 May 2009 23:00:00 +0100 2527143 http://www.medworm.com/index.php?rid=2527141&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%3D19490904%26dopt%3DAbstract Authors: Woods SC To meet the continuous demand for energy, organisms use diverse signals to match food intake with energy needs. This paper reviews the effect of satiation signals and adiposity signals on food intake, including how they interact in the brain and how their influence changes with experience. Whereas meal initiation is influenced by external environmental factors, meal size is influenced by an array of signals that can be partitioned according to their reliability in indicating caloric content of food. It is argued that the malleability of satiation signals renders them poor candidates as pharmacological targets to control body weight. PMID: 19490904 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527141 Sun, 31 May 2009 23:00:00 +0100 2527141 http://www.medworm.com/index.php?rid=2527139&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%3D19490905%26dopt%3DAbstract Authors: Wenz T, Luca C, Torraco A, Moraes CT Regulation of mitochondrial protein expression is crucial for the function of the oxidative phosphorylation (OXPHOS) system. Although the basal machinery for mitochondrial transcription is known, the regulatory mechanisms are not completely understood. Here, we characterized mTERF2, a mitochondria-localized homolog of the mitochondrial transcription termination factor mTERF1. We show that inactivation of mTERF2 in the mouse results in a myopathy and memory deficits associated with decreased levels of mitochondrial transcripts and imbalanced tRNA pool. These aberrations were associated with decreased steady-state levels of OXPHOS proteins causing a decrease in respiratory function. mTERF2 binds to the mtDNA promoter region, suggesting that i... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527139 Sun, 31 May 2009 23:00:00 +0100 2527139 http://www.medworm.com/index.php?rid=2527137&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%3D19490906%26dopt%3DAbstract We report that hypoxia-inducible factor (HIF)1alpha and PPARgamma, key mediators of glycolysis and lipid anabolism, respectively, are jointly upregulated in hypertrophic cardiomyopathy and cooperate to mediate key changes in cardiac metabolism. In response to pathologic stress, HIF1alpha activates glycolytic genes and PPARgamma, whose product, in turn, activates fatty acid uptake and glycerolipid biosynthesis genes. These changes result in increased glycolytic flux and glucose-to-lipid conversion via the glycerol-3-phosphate pathway, apoptosis, and contractile dysfunction. Ventricular deletion of Hif1alpha in mice prevents hypertrophy-induced PPARgamma activation, the consequent metabolic reprogramming, and contractile dysfunction. We propose a model in which activation of the HIF1alpha-PP... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527137 Sun, 31 May 2009 23:00:00 +0100 2527137 http://www.medworm.com/index.php?rid=2527135&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%3D19490907%26dopt%3DAbstract Authors: Dean JT, Tran L, Beaven S, Tontonoz P, Reue K, Dipple KM, Liao JC Given the success in engineering synthetic phenotypes in microbes and mammalian cells, constructing non-native pathways in mammals has become increasingly attractive for understanding and identifying potential targets for treating metabolic disorders. Here, we introduced the glyoxylate shunt into mouse liver to investigate mammalian fatty acid metabolism. Mice expressing the shunt showed resistance to diet-induced obesity on a high-fat diet despite similar food consumption. This was accompanied by a decrease in total fat mass, circulating leptin levels, plasma triglyceride concentration, and a signaling metabolite in liver, malonyl-CoA, that inhibits fatty acid degradation. Contrary to plants and bacteria, in wh... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527135 Sun, 31 May 2009 23:00:00 +0100 2527135 http://www.medworm.com/index.php?rid=2527133&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%3D19490908%26dopt%3DAbstract Authors: Huo L, Gamber K, Greeley S, Silva J, Huntoon N, Leng XH, Bjørbaek C Leptin plays a pivotal role in regulation of energy balance. Via unknown central pathways, leptin also affects peripheral glucose homeostasis and locomotor activity. We hypothesized that, specifically, pro-opiomelanocortin (POMC) neurons mediate those actions. To examine this possibility, we applied Cre-Lox technology to express leptin receptors (ObRb) exclusively in POMC neurons of the morbidly obese, profoundly diabetic, and severely hypoactive leptin receptor-deficient Lepr(db/db) mice. Here, we show that expression of ObRb only in POMC neurons leads to a marked decrease in energy intake and a modest reduction in body weight in Lepr(db/db) mice. Remarkably, blood glucose levels are entirely normalized.... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527133 Sun, 31 May 2009 23:00:00 +0100 2527133 http://www.medworm.com/index.php?rid=2527131&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%3D19490909%26dopt%3DAbstract Authors: Chen M, Wang J, Dickerson KE, Kelleher J, Xie T, Gupta D, Lai EW, Pacak K, Gavrilova O, Weinstein LS In Albright hereditary osteodystrophy, a monogenic obesity disorder linked to heterozygous mutations of G(s)alpha, the G protein that mediates receptor-stimulated cAMP generation, obesity develops only when the mutation is on the maternal allele. Likewise, mice with maternal (but not paternal) germline G(s)alpha mutation develop obesity, insulin resistance, and diabetes. These parent-of-origin effects are due to G(s)alpha imprinting, with preferential expression from the maternal allele in some tissues. As G(s)alpha is ubiquitously expressed, the tissue involved in this metabolic imprinting effect is unknown. Using brain-specific G(s)alpha knockout mice, we show that G(s)alpha ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527131 Sun, 31 May 2009 23:00:00 +0100 2527131 http://www.medworm.com/index.php?rid=2527129&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%3D19490910%26dopt%3DAbstract Authors: Sha H, He Y, Chen H, Wang C, Zenno A, Shi H, Yang X, Zhang X, Qi L Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARgamma and C/EBPalpha. Here we demonstrate that the IRE1alpha-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1alpha knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPbeta, a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1alpha is required as o... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527129 Sun, 31 May 2009 23:00:00 +0100 2527129 http://www.medworm.com/index.php?rid=2527169&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%3D19416707%26dopt%3DAbstract Authors: Gargalovic PS Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are now established features of the atherosclerotic plaque. In this issue, Thorp et al. (2009) provide initial insights into the causative relationship between UPR and the atherosclerotic disease process, specifically linking the proapoptotic mediator CHOP to plaque growth and necrosis. PMID: 19416707 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527169 Thu, 30 Apr 2009 23:00:00 +0100 2527169 http://www.medworm.com/index.php?rid=2527168&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%3D19416708%26dopt%3DAbstract Authors: Pollak M A recent report by Kalaany and Sabatini concerning mechanisms underlying the inhibitory effect of dietary restriction on the growth of certain tumors adds to the evidence that insulin and IGF-I are hormones with relevance to oncology. PMID: 19416708 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527168 Thu, 30 Apr 2009 23:00:00 +0100 2527168 http://www.medworm.com/index.php?rid=2527166&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%3D19416709%26dopt%3DAbstract Authors: Mattson MP, Maudsley S Excessive activation of the AT(1A) receptor (AT(1A)R) by angiotensin II (Ang II) is implicated in the age-related development of hypertension, diabetes, and kidney disease. AT(1A)R-deficient mice live longer and have lower levels of oxidative stress than wild-type mice (Benigni et al., 2009), suggesting a role for AT(1A)R signaling in the aging process. PMID: 19416709 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527166 Thu, 30 Apr 2009 23:00:00 +0100 2527166 http://www.medworm.com/index.php?rid=2527164&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%3D19416710%26dopt%3DAbstract Authors: Roodman GD Osteoclasts are the primary cells that resorb bone; they require high energy levels to degrade bone matrix, releasing minerals to maintain calcium homeostasis. Recent work on osteoclast differentiation and activity highlights an important role for mitochondrial biogenesis and explores the role of iron transferrin in generating a positive osteoclastogenic feedback loop. PMID: 19416710 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527164 Thu, 30 Apr 2009 23:00:00 +0100 2527164 http://www.medworm.com/index.php?rid=2527162&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%3D19416711%26dopt%3DAbstract Authors: Zhang BB, Zhou G, Li C Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a key player in regulating energy metabolism, placing it at the center stage in studies of diabetes and related metabolic diseases. Expressed in key metabolically relevant organs, AMPK is activated in response to a variety of stimuli, including cellular stress, exercise, and a wide range of hormones and agents that exert impacts on cellular metabolism. Genetic and pharmacological studies demonstrate that AMPK is required for maintaining glucose homeostasis. Activation of AMPK by pharmacological agents presents a unique challenge, given the complexity of the biology, but holds a considerable potential to reverse the metabolic abnormalities associated with type 2 diabetes. PMID: 194167... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527162 Thu, 30 Apr 2009 23:00:00 +0100 2527162 http://www.medworm.com/index.php?rid=2527159&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%3D19416712%26dopt%3DAbstract Authors: Cheng KK, Iglesias MA, Lam KS, Wang Y, Sweeney G, Zhu W, Vanhoutte PM, Kraegen EW, Xu A Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. Here we report that the endosomal adaptor protein APPL1 increases hepatic insulin sensitivity by potentiating insulin-mediated suppression of the gluconeogenic program. Insulin-stimulated activation of Akt and suppression of gluconeogenesis in hepatocytes are enhanced by APPL1 overexpression, but are attenuated by APPL1 knockdown. APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor tribble 3 (TRB3) through direct competition, thereby promoting Akt translocation to the plasma membrane and the endosomes for further activation. In db/db diabetic mice, the blocka... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527159 Thu, 30 Apr 2009 23:00:00 +0100 2527159 http://www.medworm.com/index.php?rid=2527157&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%3D19416713%26dopt%3DAbstract Authors: Wang XL, Suzuki R, Lee K, Tran T, Gunton JE, Saha AK, Patti ME, Goldfine A, Ruderman NB, Gonzalez FJ, Kahn CR We have previously shown that expression of the transcription factor ARNT/HIF1beta is reduced in islets of humans with type 2 diabetes. We have now found that ARNT is also reduced in livers of diabetics. To study the functional effect of its reduction, we created mice with liver-specific ablation (L-ARNT KO) using ARNT loxP mice and adenoviral-mediated delivery of Cre. L-ARNT KO mice had normal blood glucose but increased fed insulin levels. These mice also exhibited features of type 2 diabetes with increased hepatic gluconeogenesis, increased lipogenic gene expression, and low serum beta-hydroxybutyrate. These effects appear to be secondary to increased expression of ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527157 Thu, 30 Apr 2009 23:00:00 +0100 2527157 http://www.medworm.com/index.php?rid=2527155&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%3D19416714%26dopt%3DAbstract Authors: Jo H, Shim J, Lee JH, Lee J, Kim JB The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. We demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demonstrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementa... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527155 Thu, 30 Apr 2009 23:00:00 +0100 2527155 http://www.medworm.com/index.php?rid=2527153&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%3D19416715%26dopt%3DAbstract Authors: Fernandez-Ayala DJ, Sanz A, Vartiainen S, Kemppainen KK, Babusiak M, Mustalahti E, Costa R, Tuomela T, Zeviani M, Chung J, O'Dell KM, Rustin P, Jacobs HT Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders. The single-subunit alternative oxidase (AOX) found in many eukaryotes, but not in arthropods or vertebrates, offers a potential bypass of the OXPHOS cytochrome chain under conditions of pathological OXPHOS inhibition. We have engineered Ciona intestinalis AOX for conditional expression in Drosophila melanogaster. Ubiquitous AOX expression produced no detrimental phenotype in wild-type flies. However, mitochondrial suspensions from AOX-expressing flies exhibited a significant cyanide-resistant substrate oxidation, and the flies ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527153 Thu, 30 Apr 2009 23:00:00 +0100 2527153 http://www.medworm.com/index.php?rid=2527151&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%3D19416716%26dopt%3DAbstract Authors: Zhang DL, Hughes RM, Ollivierre-Wilson H, Ghosh MC, Rouault TA Ferroportin (FPN1), the sole characterized mammalian iron exporter, has an iron-responsive element (IRE) in its 5' untranslated region, which ensures that its translation is repressed by iron regulatory proteins (IRPs) in iron-deficient conditions to maintain cellular iron content. However, here we demonstrate that duodenal epithelial and erythroid precursor cells utilize an alternative upstream promoter to express a FPN1 transcript, FPN1B, which lacks the IRE and is not repressed in iron-deficient conditions. The FPN1B transcript encodes ferroportin with an identical open reading frame and contributes significantly to ferroportin protein expression in erythroid precursors and likely also in the duodenum of iron-st... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527151 Thu, 30 Apr 2009 23:00:00 +0100 2527151 http://www.medworm.com/index.php?rid=2527149&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%3D19416717%26dopt%3DAbstract Authors: Thorp E, Li G, Seimon TA, Kuriakose G, Ron D, Tabas I Endoplasmic reticulum (ER) stress is a hallmark of advanced atherosclerosis, but its causative role in plaque progression is unknown. In vitro studies have implicated the ER stress effector CHOP in macrophage apoptosis, a process involved in plaque necrosis in advanced atheromata. To test the effect of CHOP deficiency in vivo, aortic root lesions of fat-fed Chop+/+;Apoe-/- and Chop-/-;Apoe-/- mice were analyzed for size and morphology. Despite similar plasma lipoproteins, lesion area was 35% smaller in Chop-/-;Apoe-/- mice. Most importantly, plaque necrosis was reduced by approximately 50% and lesional apoptosis by 35% in the CHOP-deficient mice. Similar results were found in fat-fed Chop-/-;Ldlr-/- versus Chop+/+;Ldlr-/- m... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527149 Thu, 30 Apr 2009 23:00:00 +0100 2527149 http://www.medworm.com/index.php?rid=2527203&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%3D19356709%26dopt%3DAbstract Authors: Gromada J, Duttaroy A, Rorsman P Type 2 diabetes (T2DM) is not only a disorder of impaired insulin secretion but also glucagon oversecretion. However, the link between the two remains unclear. Is it possible that the latter is a consequence of the former? In this issue, Kawamori et al. (2009) have addressed this question by generating alpha cell-specific insulin receptor knockout mice. PMID: 19356709 [PubMed - indexed for MEDLINE] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527203 Tue, 31 Mar 2009 23:00:00 +0100 2527203 http://www.medworm.com/index.php?rid=2527201&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%3D19356710%26dopt%3DAbstract Authors: de Cabo R, Navas P Faced with changing food availability, organisms adapt metabolism to survive. In a recent issue of Cell, Lin et al. (2009) described the acetylation of an extranuclear enzyme being regulated by acetyl-CoA. This finding connects nutrient availability, energy status, and survival. PMID: 19356710 [PubMed - indexed for MEDLINE] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527201 Tue, 31 Mar 2009 23:00:00 +0100 2527201 http://www.medworm.com/index.php?rid=2527199&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%3D19356711%26dopt%3DAbstract Authors: Shoubridge EA Two mammalian mitochondrial transcription factors (TFB1M and TFB2M) share homology with universally expressed dimethyltransferases that modify conserved adenines in the small ribosomal subunit rRNA. Work in this issue (Metodiev et al., 2009) shows that loss of TFB1M abolishes mitochondrial ribosome assembly without affecting mitochondrial transcription. PMID: 19356711 [PubMed - indexed for MEDLINE] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527199 Tue, 31 Mar 2009 23:00:00 +0100 2527199 http://www.medworm.com/index.php?rid=2527182&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%3D19356712%26dopt%3DAbstract Authors: Stansfield I, Proud CG Hypoxia endangers the survival of cells and organisms. Mutations in an enzyme that attaches amino acids to tRNAs to supply protein synthesis confer resistance to hypoxia in C. elegans. By slowing down protein synthesis (a major consumer of energy), such mutations may save valuable energy and/or prevent accumulation of malfolded proteins. PMID: 19356712 [PubMed - indexed for MEDLINE] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527182 Tue, 31 Mar 2009 23:00:00 +0100 2527182 http://www.medworm.com/index.php?rid=2527180&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%3D19356713%26dopt%3DAbstract Authors: Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA a... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527180 Tue, 31 Mar 2009 23:00:00 +0100 2527180 http://www.medworm.com/index.php?rid=2527179&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%3D19356714%26dopt%3DAbstract Authors: Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X Hepatic metabolic derangements are key components in the development of fatty liver, insulin resistance, and atherosclerosis. SIRT1, a NAD+-dependent protein deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. Here we demonstrate that hepatic SIRT1 regulates lipid homeostasis by positively regulating peroxisome proliferators-activated receptor alpha (PPARalpha), a nuclear receptor that mediates the adaptive response to fasting and starvation. Hepatocyte-specific deletion of SIRT1 impairs PPARalpha signaling and decreases fatty acid beta-oxidation, whereas overexpression of SIRT1 induces the expression of PPARalpha targets. SIRT1 interacts with PPARalpha and is required to a... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527179 Tue, 31 Mar 2009 23:00:00 +0100 2527179 http://www.medworm.com/index.php?rid=2527177&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%3D19356715%26dopt%3DAbstract Authors: Chavey C, Lazennec G, Lagarrigue S, Clapé C, Iankova I, Teyssier J, Annicotte JS, Schmidt J, Mataki C, Yamamoto H, Sanches R, Guma A, Stich V, Vitkova M, Jardin-Watelet B, Renard E, Strieter R, Tuthill A, Hotamisligil GS, Vidal-Puig A, Zorzano A, Langin D, Fajas L We show here high levels of expression and secretion of the chemokine CXC ligand 5 (CXCL5) in the macrophage fraction of white adipose tissue (WAT). Moreover, we find that CXCL5 is dramatically increased in serum of human obese compared to lean subjects. Conversely, CXCL5 concentration is decreased in obese subjects after a weight reduction program, or in obese non-insulin-resistant, compared to insulin-resistant, subjects. Most importantly we demonstrate that treatment with recombinant CXCL5 blocks insulin-stim... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527177 Tue, 31 Mar 2009 23:00:00 +0100 2527177 http://www.medworm.com/index.php?rid=2527175&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%3D19356716%26dopt%3DAbstract In this study, we created and characterized alpha cell-specific insulin receptor knockout (alphaIRKO) mice to directly explore the role of insulin signaling in the regulation of glucagon secretion in vivo. Adult male alphaIRKO mice exhibited mild glucose intolerance, hyperglycemia, and hyperglucagonemia in the fed state and enhanced glucagon secretion in response to L-arginine stimulation. Hyperinsulinemic-hypoglycemic clamp studies revealed an enhanced glucagon secretory response and an abnormal norepinephrine response to hypoglycemia in alphaIRKO mice. The mutants also exhibited an age-dependent increase in beta cell mass. Furthermore, siRNA-mediated knockdown of insulin receptor in glucagon-secreting InR1G cells promoted enhanced glucagon secretion and complemented our in vivo findings.... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527175 Tue, 31 Mar 2009 23:00:00 +0100 2527175 http://www.medworm.com/index.php?rid=2527173&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%3D19356717%26dopt%3DAbstract Authors: Mori H, Inoki K, Münzberg H, Opland D, Faouzi M, Villanueva EC, Ikenoue T, Kwiatkowski D, MacDougald OA, Myers MG, Guan KL The mammalian target of rapamycin (mTOR) promotes anabolic cellular processes in response to growth factors and metabolic cues. The TSC1 and TSC2 tumor suppressors are major upstream inhibitory regulators of mTOR signaling. Mice with Rip2/Cre-mediated deletion of Tsc1 (Rip-Tsc1cKO mice) developed hyperphagia and obesity, suggesting that hypothalamic disruption (for which Rip2/Cre is well known) of Tsc1 may dysregulate feeding circuits via mTOR activation. Indeed, Rip-Tsc1cKO mice displayed increased mTOR signaling and enlarged neuron cell size in a number of hypothalamic populations, including Pomc neurons. Furthermore, Tsc1 deletion with Pomc/Cre (Po... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527173 Tue, 31 Mar 2009 23:00:00 +0100 2527173 http://www.medworm.com/index.php?rid=2527171&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%3D19356718%26dopt%3DAbstract Authors: Cohen M, Reale V, Olofsson B, Knights A, Evans P, de Bono M Animals modify food-seeking behavior and metabolism according to perceived food availability. Here we show that, in the roundworm C. elegans, release of neuropeptides from interneurons that are directly postsynaptic to olfactory, gustatory, and thermosensory neurons coordinately regulates behavior and metabolism. Animals lacking these neuropeptides, encoded by the flp-18 gene, are defective in chemosensation and foraging, accumulate excess fat, and exhibit reduced oxygen consumption. Two G protein-coupled receptors of the NPY/RFamide family, NPR-4 and NPR-5, are activated by FLP-18 peptides in vitro and exhibit mutant phenotypes that recapitulate those of flp-18 mutants. Our data suggest that sensory input can coordin... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527171 Tue, 31 Mar 2009 23:00:00 +0100 2527171 http://www.medworm.com/index.php?rid=2527170&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%3D19356719%26dopt%3DAbstract Authors: Metodiev MD, Lesko N, Park CB, Cámara Y, Shi Y, Wibom R, Hultenby K, Gustafsson CM, Larsson NG The 3' end of the rRNA of the small ribosomal subunit contains two extremely highly conserved dimethylated adenines. This modification and the responsible methyltransferases are present in all three domains of life, but its function has remained elusive. We have disrupted the mouse Tfb1m gene encoding a mitochondrial protein homologous to bacterial dimethyltransferases and demonstrate here that loss of TFB1M is embryonic lethal. Disruption of Tfb1m in heart leads to complete loss of adenine dimethylation of the rRNA of the small mitochondrial ribosomal subunit, impaired assembly of the mitochondrial ribosome, and abolished mitochondrial translation. In addition, we present bioch... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2527170 Tue, 31 Mar 2009 23:00:00 +0100 2527170 http://www.medworm.com/index.php?rid=2233125&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%3D19254564%26dopt%3DAbstract Authors: Fleming RE The mechanism by which HFE participates in the regulation of iron homeostasis has remained enigmatic. Gao et al. (2009) make the key discovery that the regulation of hepcidin in response to holotransferrin requires the interaction between HFE and transferrin receptor 2 (TfR2). PMID: 19254564 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233125 Sun, 01 Mar 2009 05:00:00 +0100 2233125 http://www.medworm.com/index.php?rid=2233124&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%3D19254565%26dopt%3DAbstract Authors: Stöckli J, James DE Insulin signaling is key to the etiology of metabolic syndrome. Recent work (Luan et al., 2009) uncovers a role for beta-arrestin, previously known to control GPCR desensitization, in insulin signaling. In mouse models, beta-arrestin-2 controls whole-body insulin action by regulating assembly of a complex containing insulin receptor, c-Src, and Akt. PMID: 19254565 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233124 Sun, 01 Mar 2009 05:00:00 +0100 2233124 http://www.medworm.com/index.php?rid=2233123&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%3D19254566%26dopt%3DAbstract Authors: Hernandez C, Lin JD Fructose is a highly lipogenic dietary nutrient that has been implicated in the pathogenesis of hyperlipidemia and insulin resistance. In this issue, Nagai et al. (2009) provide in vivo evidence that pinpoints transcriptional coactivator PGC-1beta as a key factor in mediating the metabolic response to fructose intake. PMID: 19254566 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233123 Sun, 01 Mar 2009 05:00:00 +0100 2233123 http://www.medworm.com/index.php?rid=2233122&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%3D19254567%26dopt%3DAbstract We report two hepatic cell lines, WIF-B cells and HepG2 cells transfected with HFE, where hepcidin expression responded to iron-loaded transferrin. The response was abolished when endogenous transferrin receptor 2 (TfR2) was suppressed or in primary hepatocytes lacking either functional TfR2 or HFE. Furthermore, transferrin-treated HepG2 cells transfected with HFE chimeras containing only the alpha3 and cytoplasmic domains could upregulate hepcidin expression. Since the HFE alpha3 domain interacts with TfR2, these results supported our finding that TfR2/HFE complex is required for transcriptional regulation of hepcidin by holo-Tf. PMID: 19254567 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233122 Sun, 01 Mar 2009 05:00:00 +0100 2233122 http://www.medworm.com/index.php?rid=2233121&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%3D19254568%26dopt%3DAbstract Authors: Palanker L, Tennessen JM, Lam G, Thummel CS Drosophila HNF4 (dHNF4) is the single ancestral ortholog of a highly conserved subfamily of nuclear receptors that includes two mammalian receptors, HNFalpha and HNFgamma, and 269 members in C. elegans. We show here that dHNF4 null mutant larvae are sensitive to starvation. Starved mutant larvae consume glycogen normally but retain lipids in their midgut and fat body and have increased levels of long-chain fatty acids, suggesting that they are unable to efficiently mobilize stored fat for energy. Microarray studies support this model, indicating reduced expression of genes that control lipid catabolism and beta-oxidation. A GAL4-dHNF4;UAS-lacZ ligand sensor can be activated by starvation or exogenous long-chain fatty acids, suggestin... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233121 Sun, 01 Mar 2009 05:00:00 +0100 2233121 http://www.medworm.com/index.php?rid=2233120&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%3D19254569%26dopt%3DAbstract Authors: Ryu D, Oh KJ, Jo HY, Hedrick S, Kim YN, Hwang YJ, Park TS, Han JS, Choi CS, Montminy M, Koo SH TORC2 is a major transcriptional coactivator for hepatic glucose production. Insulin impedes gluconeogenesis by inhibiting TORC2 via SIK2-dependent phosphorylation at Ser171. Interruption of this process greatly perturbs hepatic glucose metabolism, thus promoting hyperglycemia in rodents. Here, we show that hyperactivation of TORC2 would exacerbate insulin resistance by enhancing expression of LIPIN1, a mammalian phosphatidic acid phosphatase for diacylglycerol (DAG) synthesis. Diet-induced or genetic obesity increases LIPIN1 expression in mouse liver, and TORC2 is responsible for its transcriptional activation. While overexpression of LIPIN1 disturbs hepatic insulin signaling, knock... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233120 Sun, 01 Mar 2009 05:00:00 +0100 2233120 http://www.medworm.com/index.php?rid=2233119&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%3D19254570%26dopt%3DAbstract Authors: Nagai Y, Yonemitsu S, Erion DM, Iwasaki T, Stark R, Weismann D, Dong J, Zhang D, Jurczak MJ, Löffler MG, Cresswell J, Yu XX, Murray SF, Bhanot S, Monia BP, Bogan JS, Samuel V, Shulman GI Peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1beta) is known to be a transcriptional coactivator for SREBP-1, the master regulator of hepatic lipogenesis. Here, we evaluated the role of PGC-1beta in the pathogenesis of fructose-induced insulin resistance by using an antisense oligonucletoide (ASO) to knockdown PGC-1beta in liver and adipose tissue. PGC-1beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver. PGC-1beta ASO also reversed hepatic insulin resistance induced by ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233119 Sun, 01 Mar 2009 05:00:00 +0100 2233119 http://www.medworm.com/index.php?rid=2233118&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%3D19254571%26dopt%3DAbstract Authors: Acin-Perez R, Salazar E, Kamenetsky M, Buck J, Levin LR, Manfredi G Mitochondria constantly respond to changes in substrate availability and energy utilization to maintain cellular ATP supplies, and at the same time control reactive oxygen radical (ROS) production. Reversible phosphorylation of mitochondrial proteins has been proposed to play a fundamental role in metabolic homeostasis, but very little is known about the signaling pathways involved. We show here that protein kinase A (PKA) regulates ATP production by phosphorylation of mitochondrial proteins, including subunits of cytochrome c oxidase. The cyclic AMP (cAMP), which activates mitochondrial PKA, does not originate from cytoplasmic sources but is generated within mitochondria by the carbon dioxide/bicarbonate-regu... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233118 Sun, 01 Mar 2009 05:00:00 +0100 2233118 http://www.medworm.com/index.php?rid=2233117&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%3D19254572%26dopt%3DAbstract Authors: Qi L, Saberi M, Zmuda E, Wang Y, Altarejos J, Zhang X, Dentin R, Hedrick S, Bandyopadhyay G, Hai T, Olefsky J, Montminy M Increases in adiposity trigger metabolic and inflammatory changes that interfere with insulin action in peripheral tissues, culminating in beta cell failure and overt diabetes. We found that the cAMP Response Element Binding protein (CREB) is activated in adipose cells under obese conditions, where it promotes insulin resistance by triggering expression of the transcriptional repressor ATF3 and thereby downregulating expression of the adipokine hormone adiponectin as well as the insulin-sensitive glucose transporter 4 (GLUT4). Transgenic mice expressing a dominant-negative CREB transgene in adipocytes displayed increased whole-body insulin sensitivity in th... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233117 Sun, 01 Mar 2009 05:00:00 +0100 2233117 http://www.medworm.com/index.php?rid=2233116&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%3D19254573%26dopt%3DAbstract Authors: Wang Y, Sul HS Pref-1 is an EGF repeat-containing transmembrane protein that produces a biologically active soluble form by TACE-mediated cleavage. Although Pref-1 inhibition of adipogenesis has been well established, the specific target(s) of Pref-1 or the Pref-1 function in mesenchymal cell commitment/differentiation are not known. Here, we show that Sox9 downregulation is required for adipocyte differentiation and that Pref-1 inhibits adipocyte differentiation through upregulating Sox9 expression. Sox9 directly binds to the promoter regions of C/EBPbeta and C/EBPdelta to suppress their promoter activity, preventing adipocyte differentiation. Furthermore, we also show that, by inducing Sox9, Pref-1 promotes chondrogenic induction of mesenchymal cells but prevents chondrocyte... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2233116 Sun, 01 Mar 2009 05:00:00 +0100 2233116 http://www.medworm.com/index.php?rid=2160482&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%3D19187768%26dopt%3DAbstract Authors: Lodhi IJ, Semenkovich CF Mitochondrial uncoupling protein 1 (UCP1) is a key regulator of adaptive thermogenesis and energy expenditure. Mice lacking UCP1 are cold sensitive, but surprisingly not obese at room temperature. In this issue of Cell Metabolism, Feldmann et al. (2009) unmask an obesogenic phenotype by simply maintaining these mice at thermoneutrality. PMID: 19187768 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160482 Sun, 01 Feb 2009 05:00:00 +0100 2160482 http://www.medworm.com/index.php?rid=2160481&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%3D19187769%26dopt%3DAbstract Authors: Cunningham KA, Ashrafi K The fundamental task of maintaining energy balance is complex when nutrient levels are plentiful, but it becomes even more challenging when nutrients are dynamic or scarce. A recent Nature report delineates a role of the AMP kinase pathway in rationing energy stores for the long-term survival of Caenorhabditis elegans dauers (Narbonne and Roy, 2009). PMID: 19187769 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160481 Sun, 01 Feb 2009 05:00:00 +0100 2160481 http://www.medworm.com/index.php?rid=2160480&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%3D19187770%26dopt%3DAbstract Authors: Myers MG, Münzberg H, Leinninger GM, Leshan RL Leptin signals the repletion of fat stores, acting in the CNS to permit energy utilization by a host of autonomic and neuroendocrine processes and to decrease feeding. While much recent research has focused on the leptin-regulated circuitry of the hypothalamic arcuate nucleus (ARC), the majority of brain leptin receptor (LepRb)-expressing neurons lie outside the ARC in other CNS regions known to modulate energy balance. Each set of LepRb neurons throughout the brain presumably mediates unique aspects of leptin action, and understanding the function for LepRb-expressing neurons throughout the brain represents a crucial next step in the study of energy homeostasis. PMID: 19187770 [PubMed - in process] (Source: Cell Metaboli... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160480 Sun, 01 Feb 2009 05:00:00 +0100 2160480 http://www.medworm.com/index.php?rid=2160479&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%3D19187771%26dopt%3DAbstract In this study, we found that the interferon gamma-inducible protein 10 plays an important role in triggering beta cell destruction. Islets isolated from patients with T2DM secreted CXCL10 and contained 33.5-fold more CXCL10 mRNA than islets from control patients. Pancreatic sections from obese nondiabetic individuals and patients with T2DM and T1DM expressed CXCL10 in beta cells. Treatment of human islets with CXCL10 decreased beta cell viability, impaired insulin secretion, and decreased insulin mRNA. CXCL10 induced sustained activation of Akt, JNK, and cleavage of p21-activated protein kinase 2 (PAK-2), switching Akt signals from proliferation to apoptosis. These effects were not mediated by the commonly known CXCL10 receptor CXCR3 but through TLR4. Our data suggest CXCL10 as a binding p... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160479 Sun, 01 Feb 2009 05:00:00 +0100 2160479 http://www.medworm.com/index.php?rid=2160478&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%3D19187772%26dopt%3DAbstract Authors: Remedi MS, Kurata HT, Scott A, Wunderlich FT, Rother E, Kleinridders A, Tong A, Brüning JC, Koster JC, Nichols CG ATP-insensitive K(ATP) channel mutations cause neonatal diabetes mellitus (NDM). To explore the mechanistic etiology, we generated transgenic mice carrying an ATP-insensitive mutant K(ATP) channel subunit. Constitutive expression in pancreatic beta cells caused neonatal hyperglycemia and progression to severe diabetes and growth retardation, with loss of islet insulin content and beta cell architecture. Tamoxifen-induced expression in adult beta cells led to diabetes within 2 weeks, with similar secondary consequences. Diabetes was prevented by transplantation of normal islets under the kidney capsule. Moreover, the endogenous islets maintained normal insulin ... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160478 Sun, 01 Feb 2009 05:00:00 +0100 2160478 http://www.medworm.com/index.php?rid=2160477&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%3D19187773%26dopt%3DAbstract Authors: Cortés VA, Curtis DE, Sukumaran S, Shao X, Parameswara V, Rashid S, Smith AR, Ren J, Esser V, Hammer RE, Agarwal AK, Horton JD, Garg A Mutations in 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2) cause congenital generalized lipodystrophy. To understand the molecular mechanisms underlying the metabolic complications associated with AGPAT2 deficiency, Agpat2 null mice were generated. Agpat2(-/-) mice develop severe lipodystrophy affecting both white and brown adipose tissue, extreme insulin resistance, diabetes, and hepatic steatosis. The expression of lipogenic genes and rates of de novo fatty acid biosynthesis were increased approximately 4-fold in Agpat2(-/-) mouse livers. The mRNA and protein levels of monoacylglycerol acyltransferase isoform 1 were markedly in... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160477 Sun, 01 Feb 2009 05:00:00 +0100 2160477 http://www.medworm.com/index.php?rid=2160476&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%3D19187774%26dopt%3DAbstract Authors: Ye J, Li JZ, Liu Y, Li X, Yang T, Ma X, Li Q, Yao Z, Li P Secretion of triacylglycerol-enriched very-low-density lipoproteins (VLDLs) from the liver is vital for maintaining plasma lipid homeostasis. However, the process of VLDL assembly and lipidation is not well characterized. Here, we observed that liver of Cideb null mice had higher levels of triacylglycerols accompanied by low level of VLDL secretion. Furthermore, VLDL particles secreted from hepatocytes of Cideb null mice have low levels of triacylglycerols but normal levels of apoB. We also observed that Cideb is localized to endoplasmic reticulum and lipid droplets. Importantly, we have identified apoB as a Cideb-interacting protein. By infecting adenoviruses expressing various Cideb truncations into hepatocytes of Cid... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160476 Sun, 01 Feb 2009 05:00:00 +0100 2160476 http://www.medworm.com/index.php?rid=2160475&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%3D19187775%26dopt%3DAbstract Authors: Sakakibara I, Fujino T, Ishii M, Tanaka T, Shimosawa T, Miura S, Zhang W, Tokutake Y, Yamamoto J, Awano M, Iwasaki S, Motoike T, Okamura M, Inagaki T, Kita K, Ezaki O, Naito M, Kuwaki T, Chohnan S, Yamamoto TT, Hammer RE, Kodama T, Yanagisawa M, Sakai J Acetate is activated to acetyl-CoA by acetyl-CoA synthetase 2 (AceCS2), a mitochondrial enzyme. Here, we report that the activation of acetate by AceCS2 has a specific and unique role in thermogenesis during fasting. In the skeletal muscle of fasted AceCS2(-/-) mice, ATP levels were reduced by 50% compared to AceCS2(+/+) mice. Fasted AceCS2(-/-) mice were significantly hypothermic and had reduced exercise capacity. Furthermore, when fed a low-carbohydrate diet, 4-week-old weaned AceCS2(-/-) mice also exhibited hypothermia accom... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160475 Sun, 01 Feb 2009 05:00:00 +0100 2160475 http://www.medworm.com/index.php?rid=2160474&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%3D19187776%26dopt%3DAbstract Authors: Feldmann HM, Golozoubova V, Cannon B, Nedergaard J As original studies of UCP1-ablated mice failed to demonstrate an obesogenic effect, alternative mechanisms for adaptive adrenergic thermogenesis have been sought. However, we demonstrate here that in C57Bl6 mice exempt from thermal stress (i.e., kept at thermoneutrality), UCP1 ablation in itself induced obesity, even in mice fed control diet, and vastly augmented diet-induced obesity (high-fat diet); i.e., the mice exhibited increased metabolic efficiency. In wild-type mice, high-fat diet increased norepinephrine-induced thermogenesis; i.e., diet-induced thermogenesis was observed, but no such effect was observed in UCP1-ablated mice, demonstrating that diet-induced thermogenesis fully emanates from UCP1 activity. We conclude... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2160474 Sun, 01 Feb 2009 05:00:00 +0100 2160474 http://www.medworm.com/index.php?rid=2112242&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%3D19147412%26dopt%3DAbstract Authors: Shah YM, Matsubara T, Ito S, Yim SH, Gonzalez FJ Iron deficiency and iron overload are among the most prevalent nutritional disorders worldwide. Duodenal cytochrome b (DcytB) and divalent metal transporter 1 (DMT1) are regulators of iron absorption. Their expression is increased during high systemic requirements for iron, but the molecular mechanisms that regulate DcytB and DMT1 expression are undefined. Hypoxia-inducible factor (HIF) signaling was induced in the intestine following acute iron deficiency in the duodenum, resulting in activation of DcytB and DMT1 expression and an increase in iron uptake. DcytB and DMT1 were demonstrated as direct HIF-2alpha target genes. Genetic disruption of HIF signaling in the intestine abolished the adaptive induction of iron absorption fo... Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2112242 Tue, 13 Jan 2009 05:00:00 +0100 2112242 http://www.medworm.com/index.php?rid=2087038&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%3D19117540%26dopt%3DAbstract Authors: Moss LG, Newgard CB Pancreatic islet beta cell mass expands in response to certain physiological conditions such as pregnancy and obesity, but the signaling pathways involved are not well understood. Possible insights come from a newly described regulatory circuit through which obesity-enhanced kinase signaling in the liver triggers expansion of islet mass and enhanced insulin secretion. PMID: 19117540 [PubMed - in process] (Source: Cell Metabolism) Cell Metabolism journals http://www.medworm.com/rss/comments.php?id=2087038 Wed, 07 Jan 2009 05:00:00 +0100 2087038