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Physiological Genomics

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https://www.readbyqxmd.com/read/29127223/systems-genetic-analysis-of-brown-adipose-tissue-function
#1
Michal Pravenec, Laura Saba, Vaclav Zidek, Vladimir Landa, Petr Mlejnek, Jan Silhavy, Miroslava Simakova, Hynak Strnad, Jaroslava Trnovska, Vojtech Skop, Martina Huttl, Irena Markova, Olena Oliyarnyk, Hana Malinska, Ludmila Kazdova, Harry Smith, Boris Tabakoff
Brown adipose tissue (BAT) has been suggested to play an important role in lipid and glucose metabolism in rodents and possibly also in humans. In the current study, we used genetic and correlation analyses in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), to identify genetic determinants of BAT function. Linkage analyses revealed a quantitative trait locus (QTL) associated with interscapular BAT mass on chromosome 4 and two closely linked QTLs associated with glucose oxidation and glucose incorporation into BAT lipids on chromosome 2...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127222/mef2-transcription-factors-in-human-placenta-and-involvement-in-cytotrophoblast-invasion-and-differentiation
#2
Lucy Li, Lewis P Rubin, Xiaoming Gong
Development of the human placenta and its trophoblast cell types is critical for successful pregnancy. Defects in trophoblast invasion and differentiation are associated with adverse pregnancy outcomes, including preeclampsia. The members of myocyte enhancer factor-2 (MEF2) family of transcription factors are key regulators of cellular proliferation, differentiation, and invasion in various cell types and tissues and might play a similarly important role in regulating trophoblast proliferation, invasion, and differentiation during human placental development...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127221/genetics-of-metabolic-syndrome-potential-clues-from-wild-derived-inbred-mouse-strains
#3
Subashini Karunakaran, Susanne Michelle Clee
The metabolic syndrome (MetS) is a complex constellation of metabolic abnormalities including obesity, abnormal glucose metabolism, dyslipidemia, and elevated blood pressure that together substantially increase risk for cardiovascular disease and type 2 diabetes. Both genetic and environmental factors contribute to the development of MetS, but this process is still far from understood. Human studies have revealed only part of the underlying basis. Studies in mice offer many strengths that can complement human studies to help elucidate the etiology and pathophysiology of MetS...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29127220/therapeutic-potential-of-micrornas-for-the-treatment-of-renal-fibrosis-and-ckd
#4
Wenshan Lv, Fan Fan, Yangang Wang, Ezekiel Gonzalez-Fernandez, Chen Wang, Lili Yang, George W Booz, Richard J Roman
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD...
November 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29093195/the-effect-of-high-fat-diet-on-secreted-milk-transcriptome-in-mid-lactation-mice
#5
Yulu Chen, Junhui Wang, Shiqi Yang, Sagar Utturkar, Jennifer Crodian, Shelby Cummings, Jyothi Thimmapuram, Phillip San Miguel, Shihuan Kuang, Michael Gribskov, Karen Plaut, Theresa Casey
High fat diet (HFD) during lactation alters milk composition and is associated with development of metabolic diseases in the offspring. We hypothesized that HFD affects milk microRNA (miRNA) and mRNA content, which potentially impact offspring development. Our objective was to determine the effect of maternal HFD on secreted milk transcriptome. To meet this objective, 4-week old female ICR mice were divided into two treatment groups: control diet (CD) containing 10% kcal fat and HFD containing 60% kcal fat...
November 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29093194/distribution-and-function-of-the-muscarinic-receptor-subtypes-in-the-cardiovascular-system
#6
Hannah C Saternos, Daniyah A Almarghalani, Hayley M Gibson, Mahmood A Meqdad, Raymond B Antypas, Ajay Lingireddy, Wissam A AbouAlaiwi
Muscarinic acetylcholine receptors belong to the G-protein coupled receptor superfamily and are widely known to mediate numerous functions within the central and peripheral nervous system. Thus, they have become attractive therapeutic targets for various disorders. It has long been known that the parasympathetic system, governed by acetylcholine, plays an essential role in regulating cardiovascular function. Unfortunately, due to the lack of pharmacologic selectivity for any one muscarinic receptor, there was a minimal understanding of their distribution and function within this region...
November 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29030493/intrinsic-aerobic-capacity-governs-the-associations-between-gut-microbiota-composition-and-fat-metabolism-age-dependently-in-rat-siblings
#7
Satu Pekkala, Sanna Lensu, Miriam Nokia, Sanja Vanhatalo, Lauren G Koch, Steven L Britton, Heikki Kainulainen
Host genetic factors affecting the gut microbiome play an important role in obesity. Yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity while in older adult (hereafter old) rats most of the differences between the lines associated with body weight...
October 13, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28986397/potential-mechanisms-of-hypothalamic-renin-angiotensin-system-activation-by-leptin-and-doca-salt-for-the-control-of-resting-metabolism
#8
Sarah A Sapouckey, Guorui Deng, Curt D Sigmund, Justin L Grobe
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 autonomic and energy expenditure responses to various stimuli including deoxycorticosterone acetate (DOCA)-salt, high fat feeding, and leptin...
October 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28986396/ace-modulated-adiposity-is-related-to-higher-energy-expenditure-and-independent-of-lipolysis-and-glucose-incorporation-into-lipids-in-adipocytes
#9
Miriam Helena Fonseca-Alaniz, Talita Sayuri Higa, Tarcila Beatriz Ferraz-de-Campos, Julie Takada, Francisco L Torres-Leal, Fabiana Sant'Anna Evangelista, Fabio B Lima, José Eduardo Krieger
Emerging evidence suggests that both systemic and white adipose tissue (WAT)-renin-angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. 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-week follow-up period, transgenic mice harboring 3 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 1 ACE gene copy (1ACE) after long fasting (12-hour)...
October 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28972038/comparative-transcriptome-and-histological-analyses-provide-insights-into-the-prenatal-skin-pigmentation-in-goat-capra-hircus
#10
Hangxing Ren, Gaofu Wang, Jing Jiang, Jie Li, Lin Fu, Liangjia Liu, Nianfu Li, Jinhong Zhao, Xiaoyan Sun, Li Zhang, Haiyan Zhang, Peng Zhou
The Youzhou dark goat is the natural mutant characterizing the dark skin of 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 using deep RNA-sequencing, qPCR, 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...
September 29, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28939645/cyclooxygenase-2-protein-protein-interactions-and-posttranslational-modifications
#11
Anna Alexanian, Andrey Sorokin
Numerous studies implicate the COX2 enzyme and COX2- derived prostanoids in various human diseases, and as such, 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 post-transcriptional levels, leading to the development of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX2 inhibitors (COXIBs), which inhibit the COX2 enzyme through direct targeting. Recently, evidence of post-translational regulation of COX2 enzymatic activity by s-nitrosylation, glycosylation and phosphorylation has also been presented...
September 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28939644/role-of-lysophosphatidic-acid-and-its-receptors-in-the-kidney
#12
Frank Park, Duane Miller
Lysophosphatidic acid (LPA) is a bioactive phospholipid, which can exert diverse biological effects in various diseased states of the kidney by activating at least 6 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, recruit immune cells to the site of injury, and stimulate pro-fibrotic signaling by increasing gene transcription...
September 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28939643/role-of-g-protein-coupled-receptor-kinase-6-in-escherichia-coli-lung-infection-model-in-mice
#13
Taehyung Lee, Nandakumar Packiriswamy, Eunhee Lee, Peter C Lucas, Laura R McCabe, Narayanan Parameswaran
G protein-coupled receptor kinase-6 (GRK6) is a serine/threonine kinase that is important in inflammatory processes. In this study, we examined the role of GRK6 in Escherichia coli (E. 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 to 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...
September 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28916635/the-genetics-of-hypertension-an-assessment-of-progress-in-the-spontaneously-hypertensive-rat
#14
Peter A Doris
The application of gene mapping methods to uncover the genetic basis of hypertension in the inbred spontaneously hypertensive rat (SHR) began over 25 years 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...
September 15, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28916634/ppar%C3%AE-and-retinol-binding-protein-7-form-a-regulatory-hub-promoting-antioxidant-properties-of-the-endothelium
#15
Addison W Woll, Frederick W Quelle, Curt D Sigmund
Peroxisome Proliferator-Activated Receptors (PPARs) are a family of conserved ligand-activated nuclear receptor transcription factors heterogeneously expressed in mammalian tissues. PPARγ is recognized as a master regulator of adipogenesis, fatty acid metabolism, and glucose homeostasis, but genetic evidence also supports the concept that PPARγ regulates the cardiovascular system, particularly vascular function and blood pressure. There is now compelling evidence that the beneficial blood pressure lowering effects of PPARγ activation are due to its activity in vascular smooth muscle and endothelium, through its modulation of nitric oxide-dependent vasomotor function...
September 15, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28916632/tissue-sex-and-age-specific-dna-methylation-of-rat-glucocorticoid-receptor-gene-promoter-and-insulin-like-growth-factor-2-imprinting-control-region
#16
Ogechukwu Brenda Agba, Ludwig Lausser, Klaus Huse, Christoph Bergmeier, Niels Jahn, Marco Groth, Martin Bens, Arne Sahm, Maria Gall, Otto W Witte, Hans A Kestler, Matthias Schwab, Matthias Platzer
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...
September 15, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28887370/genome-reprogramming-in-saccharomyces-cerevisiae-upon-nonylphenol-exposure
#17
Ceyhun Bereketoglu, Kazim Yalcin Arga, Serpil Eraslan, Bulent Mertoglu
Bioaccumulative environmental estrogen, nonylphenol (NP; 4-nonylphenol), is widely used as a non-ionic surfactant and can affect human health. Since genomes of Saccharomyces cerevisiae and higher eukaryotes share many structural and functional similarities, we investigated subcellular effects of NP on S. cerevisiae BY4742 cells by analyzing genome-wide transcriptional profiles. We examined effects of low (1 mg/L NP) and high (5 mg/L NP) 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...
September 8, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28887369/genetic-mechanisms-of-human-hypertension-and-their-implications-for-blood-pressure-physiology
#18
Eric Seidel, Ute I Scholl
Hypertension, or elevated blood pressure, constitutes a major public health burden that affects more than 1 billion people worldwide and contributes to about 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 pressure regulation, emphasizing renal salt handling and the renin angiotensin aldosterone system as players in the determination of blood pressure...
September 8, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28887368/segment-specific-responses-of-intestinal-epithelium-transcriptome-to-in-feed-antibiotics-in-pigs
#19
Kaifan Yu, Chunlong Mu, Yuxiang Yang, Yong Su, Wei-Yun Zhu
Despite widespread use of antibiotics for treatment of human diseases and promotion of growth of agricultural animals, our understanding of their effects on the host is still very limited. We used a pig model fed with a cocktail of antibiotics or without, and found based on the denaturing gradient gel electrophoresis (DGGE) patterns that the fecal bacteria from the treatment and control animals were distinct. Furthermore, the total bacterial population in the feces tended to be decreased by the antibiotic treatment (P=0...
September 8, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28916633/systems-genetics-identifies-a-co-regulated-module-of-liver-micrornas-associated-with-plasma-ldl-cholesterol-in-murine-diet-induced-dyslipidemia
#20
Alisha R Coffey, Tangi L Smallwood, Jody Albright, Kunjie Hua, Matt Kanke, Daniel Pomp, Brian J Bennett, Praveen Sethupathy
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...
November 1, 2017: Physiological Genomics
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