Potential mechanisms of hypothalamic renin-angiotensin system activation by leptin and DOCA-salt for the control of resting metabolism
The renin-angiotensin system (RAS), originally described as a circulating hormone system, is an enzymatic cascade in which the final vasoactive peptide angiotensin II (ANG) regulates cardiovascular, hydromineral, and metabolic functions. The RAS is also synthesized locally in a number of tissues including the brain, where it can act in a paracrine fashion to regulate blood pressure, thirst, fluid balance, and resting energy expenditure/resting metabolic rate (RMR). Recent studies demonstrate that ANG AT1A receptors (Agtr1a) specifically in agouti-related peptide (AgRP) neurons of the arcuate nucleus (ARC) coordinate autono...
Source: Physiological Genomics - December 5, 2017 Category: Genetics & Stem Cells Authors: Sapouckey, S. A., Deng, G., Sigmund, C. D., Grobe, J. L. Tags: Review Source Type: research
ACE-modulated adiposity is related to higher energy expenditure and independent of lipolysis and glucose incorporation into lipids in adipocytes
In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12 wk follow-up period, transgenic mice harboring three ACE (3ACE) gene copies displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (Vo2) in comparison with animals with one ACE gene copy (1ACE) after long fasting (12 h). No differences were found in food intake and in the rates of lipolysis and glucose incorporation into lipids in adipocytes. To ...
Source: Physiological Genomics - December 1, 2017 Category: Genetics & Stem Cells Authors: Fonseca-Alaniz, M. H., Higa, T. S., Ferraz-de-Campos, T. B., Takada, J., Torres-Leal, F. L., Evangelista, F. S., Lima, F. B., Krieger, J. E. Tags: Research Articles Source Type: research
Comparative transcriptome and histological analyses provide insights into the prenatal skin pigmentation in goat (Capra hircus)
The Youzhou dark goat is a natural mutant with dark skin over the whole body including the visible mucous membranes. In the present study, we characterized 100-day-old fetal skin at the histomorphological and transcriptomic levels in dark-skinned (Youzhou dark goat) and white-skinned (Yudong white goat) goats with deep RNA sequencing, quantitative PCR, and histological methods. Histological analysis indicated that there were marked differences in both melanin distribution and epidermal ultrastructure between the hyperpigmented and normal skin in two breeds of goat. Subsequent analyses suggested that a presumed structure va...
Source: Physiological Genomics - December 1, 2017 Category: Genetics & Stem Cells Authors: Ren, H., Wang, G., Jiang, J., Li, J., Fu, L., Liu, L., Li, N., Zhao, J., Sun, X., Zhang, L., Zhang, H., Zhou, P. Tags: Research Articles Source Type: research
Tissue-, sex-, and age-specific DNA methylation of rat glucocorticoid receptor gene promoter and insulin-like growth factor 2 imprinting control region
Tissue-, sex-, and age-specific epigenetic modifications such as DNA methylation are largely unknown. Changes in DNA methylation of the glucocorticoid receptor gene (NR3C1) and imprinting control region (ICR) of IGF2 and H19 genes during the lifespan are particularly interesting since these genes are susceptible to epigenetic modifications by prenatal stress or malnutrition. They are important regulators of development and aging. Methylation changes of NR3C1 affect glucocorticoid receptor expression, which is associated with stress sensitivity and stress-related diseases predominantly occurring during aging. Methylation ch...
Source: Physiological Genomics - November 14, 2017 Category: Genetics & Stem Cells Authors: Agba, O. B., Lausser, L., Huse, K., Bergmeier, C., Jahn, N., Groth, M., Bens, M., Sahm, A., Gall, M., Witte, O. W., Kestler, H. A., Schwab, M., Platzer, M. Tags: Research Articles Source Type: research
Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice
In this study, we examined the role of GRK6 in Escherichia coli-induced lung infection and inflammation using GRK6 knockout (KO) and wild-type (WT) mice. Intratracheal instillation of E. coli significantly enhanced bacterial load in the bronchoalveolar lavage (BAL) of KO compared with WT mice. Reduced bacterial clearance in the KO mice was not due to an intrinsic defect in neutrophil phagocytosis or killing but as a result of reduced neutrophil numbers in the KO BAL. Interestingly, neutrophil numbers in the lung were increased in the KO compared with WT mice, suggesting a potential dysfunction in transepithelial migration ...
Source: Physiological Genomics - November 14, 2017 Category: Genetics & Stem Cells Authors: Lee, T., Packiriswamy, N., Lee, E., Lucas, P. C., McCabe, L. R., Parameswaran, N. Tags: Research Articles Source Type: research
Cyclooxygenase 2: protein-protein interactions and posttranslational modifications
Numerous studies implicate the cyclooxygenase 2 (COX2) enzyme and COX2-derived prostanoids in various human diseases, and thus, much effort has been made to uncover the regulatory mechanisms of this enzyme. COX2 has been shown to be regulated at both the transcriptional and posttranscriptional levels, leading to the development of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX2 inhibitors (COXIBs), which inhibit the COX2 enzyme through direct targeting. Recently, evidence of posttranslational regulation of COX2 enzymatic activity by s-nitrosylation, glycosylation, and phosphorylation has also been presente...
Source: Physiological Genomics - November 14, 2017 Category: Genetics & Stem Cells Authors: Alexanian, A., Sorokin, A. Tags: Review Source Type: research
Role of lysophosphatidic acid and its receptors in the kidney
Lysophosphatidic acid (LPA) is a bioactive phospholipid that can exert diverse biological effects in various diseased states of the kidney by activating at least six cognate G protein-coupled receptors and its complex network of heterotrimeric G proteins. In many models of acute and chronic kidney injury, pathological elevations in LPA promotes abnormal changes in renal tubular epithelial cell architecture by activating apoptotic signaling, recruits immune cells to the site of injury, and stimulates profibrotic signaling by increasing gene transcription. In renal cancers, LPA can promote vascular cell proliferation and tum...
Source: Physiological Genomics - November 3, 2017 Category: Genetics & Stem Cells Authors: Park, F., Miller, D. D. Tags: Review Source Type: research
PPAR{gamma} and retinol binding protein 7 form a regulatory hub promoting antioxidant properties of the endothelium
Peroxisome proliferator-activated receptors (PPARs) are a family of conserved ligand-activated nuclear receptor transcription factors heterogeneously expressed in mammalian tissues. PPAR is recognized as a master regulator of adipogenesis, fatty acid metabolism, and glucose homeostasis, but genetic evidence also supports the concept that PPAR regulates the cardiovascular system, particularly vascular function and blood pressure. There is now compelling evidence that the beneficial blood pressure-lowering effects of PPAR activation are due to its activity in vascular smooth muscle and endothelium, through its modulation of ...
Source: Physiological Genomics - November 3, 2017 Category: Genetics & Stem Cells Authors: Woll, A. W., Quelle, F. W., Sigmund, C. D. Tags: Review Source Type: research
Genetic mechanisms of human hypertension and their implications for blood pressure physiology
Hypertension, or elevated blood pressure, constitutes a major public health burden that affects more than 1 billion people worldwide and contributes to ~9 million deaths annually. Hereditary factors are thought to contribute to up to 50% of interindividual blood pressure variability. Blood pressure in the general population approximately shows a normal distribution and is thought to be a polygenic trait. In rare cases, early-onset hypertension or hypotension are inherited as Mendelian traits. The identification of the underlying Mendelian genes and variants has contributed to our understanding of the physiology of blood pr...
Source: Physiological Genomics - November 1, 2017 Category: Genetics & Stem Cells Authors: Seidel, E., Scholl, U. I. Tags: Review Source Type: research
Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia
Chronically altered levels of circulating lipids, termed dyslipidemia, is a significant risk factor for a number of metabolic and cardiovascular morbidities. MicroRNAs (miRNAs) have emerged as important regulators of lipid balance, have been implicated in dyslipidemia, and have been proposed as candidate therapeutic targets in lipid-related disorders including atherosclerosis. A major limitation of most murine studies of miRNAs in lipid metabolic disorders is that they have been performed in just one (or very few) inbred strains, such as C57BL/6. Moreover, although individual miRNAs have been associated with lipid phenotyp...
Source: Physiological Genomics - November 1, 2017 Category: Genetics & Stem Cells Authors: Coffey, A. R., Smallwood, T. L., Albright, J., Hua, K., Kanke, M., Pomp, D., Bennett, B. J., Sethupathy, P. Tags: Research Articles Source Type: research
Genetics of hypertension: an assessment of progress in the spontaneously hypertensive rat
The application of gene mapping methods to uncover the genetic basis of hypertension in the inbred spontaneously hypertensive rat (SHR) began over 25 yr ago. This animal provides a useful model of genetic high blood pressure, and some of its features are described. In particular, it appears to be a polygenic model of disease, and polygenes participate in human hypertension genetic risk. The SHR hypertension alleles were fixed rapidly by selective breeding in just a few generations and so are presumably common genetic variants present in the outbred Wistar strain from which SHR was created. This review provides a background...
Source: Physiological Genomics - November 1, 2017 Category: Genetics & Stem Cells Authors: Doris, P. A. Tags: Review Source Type: research
Dietary fat modulation of hepatic lipase variant -514 C/T for lipids: a crossover randomized dietary intervention trial in Caribbean Hispanics
The hepatic lipase (LIPC) locus is a well-established determinant of high-density lipoprotein cholesterol (HDL-C) concentrations, an association that is modified by dietary fat in observational studies. Dietary interventions are lacking. We investigated dietary modulation of LIPC rs1800588 (–514 C/T) for lipids and glucose using a randomized crossover design comparing a high-fat Western diet and a low-fat traditional Hispanic diet in individuals of Caribbean Hispanic descent (n = 42, 4 wk/phase). No significant gene-diet interactions were observed for HDL-C. However, differences in dietary response according to LIPC ...
Source: Physiological Genomics - October 17, 2017 Category: Genetics & Stem Cells Authors: Smith, C. E., Van Rompay, M. I., Mattei, J., Garcia, J. F., Garcia-Bailo, B., Lichtenstein, A. H., Tucker, K. L., Ordovas, J. M. Tags: Research Articles Source Type: research
Segment-specific responses of intestinal epithelium transcriptome to in-feed antibiotics in pigs
This study reveals segment-specific responses of host intestinal epithelium to in-feed antibiotics, which can be a valuable resource for deciphering antibiotic-microbiota-host interactions. (Source: Physiological Genomics)
Source: Physiological Genomics - October 5, 2017 Category: Genetics & Stem Cells Authors: Yu, K., Mu, C., Yang, Y., Su, Y., Zhu, W. Tags: Research Articles Source Type: research
Germline genetic variants with implications for disease risk and therapeutic outcomes
Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are divers...
Source: Physiological Genomics - October 5, 2017 Category: Genetics & Stem Cells Authors: Pasternak, A. L., Ward, K. M., Luzum, J. A., Ellingrod, V. L., Hertz, D. L. Tags: Review Source Type: research
Genome reprogramming in Saccharomyces cerevisiae upon nonylphenol exposure
We examined effects of low (1 mg/l; <15% cell number reduction) and high (5 mg/l; >65% cell number reduction) inhibitory concentration exposures for 120 or 180 min. After 120 and 180 min of 1 mg/l NP exposure, 187 (63 downregulated, 124 upregulated) and 103 genes (56 downregulated, 47 upregulated), respectively, were differentially expressed. Similarly, 678 (168 repressed, 510 induced) and 688 genes (215 repressed, 473 induced) were differentially expressed in cells exposed to 5 mg/l NP for 120 and 180 min, respectively. Only 15 downregulated and 63 upregulated genes were common between low and high NP inhibitory con...
Source: Physiological Genomics - October 1, 2017 Category: Genetics & Stem Cells Authors: Bereketoglu, C., Arga, K. Y., Eraslan, S., Mertoglu, B. Tags: Research Articles Source Type: research
