A transcriptomic analysis of a Caucasian family cohort of high risks for the metabolic syndrome [HumanWG-6 v2.0]
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ABSTRACT: Metabolic Syndrome (MetS) is a strong predictor for diabetes and cardiovascular disease and is defined by a constellation of phenotypes including increased and adverse body fat distribution, insulin resistance, abnormalities in lipids and lipoproteins, malfunctional cardiovascular performance, and abnormal levels of adipokines and cytokines. We assayed in a subset of our family cohort phentoyped for MetS phentoypes, the genome-wde transcript levels using the Illumina Human WG-6 v2 expression arrays. Genome-wide gene expression was assayed in members of families that originally contribute to linkage signals in a previous genome-wide linkage scans for multiple MetS phenotypes.
Project description:Metabolic Syndrome (MetS) is a strong predictor for diabetes and cardiovascular disease and is defined by a constellation of phenotypes including increased and adverse body fat distribution, insulin resistance, abnormalities in lipids and lipoproteins, malfunctional cardiovascular performance, and abnormal levels of adipokines and cytokines. We assayed in a subset of our family cohort phentoyped for MetS phentoypes, the genome-wde transcript levels using the Illumina Human WG-6 v3 expression arrays. Genome-wide gene expression was assayed in members of families that originally contribute to linkage signals in a previous genome-wide linkage scans for multiple MetS phenotypes.
Project description:Metabolic Syndrome (MetS) is a strong predictor for diabetes and cardiovascular disease and is defined by a constellation of phenotypes including increased and adverse body fat distribution, insulin resistance, abnormalities in lipids and lipoproteins, malfunctional cardiovascular performance, and abnormal levels of adipokines and cytokines. We assayed in a subset of our family cohort phentoyped for MetS phentoypes, the genome-wde transcript levels using the Illumina Human WG-6 v3 expression arrays.
Project description:Metabolic Syndrome (MetS) is a strong predictor for diabetes and cardiovascular disease and is defined by a constellation of phenotypes including increased and adverse body fat distribution, insulin resistance, abnormalities in lipids and lipoproteins, malfunctional cardiovascular performance, and abnormal levels of adipokines and cytokines. We assayed in a subset of our family cohort phentoyped for MetS phentoypes, the genome-wde transcript levels using the Illumina Human WG-6 v2 expression arrays.
Project description:The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders. The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet–feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)–induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat). Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery. These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.
Project description:The metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Project description:Metabolic syndrome (MetS), a cluster of metabolic abnormalities that occur concurrently that significantly increases the risk of cardiovascular disease and mortality. 3-mercaptopyruvate sulfurtransferase (MPST), a cysteine-catabolizing enzyme that yields pyruvate and hydrogen sulfide (H2S), plays a central role in the regulation of energy homeostasis. Herein, we seek to investigate the role of MPST/H2S in MetS using a mouse model of the disease.Wilt type (WT) mice were fed a high-fat diet (HFD) for 15 weeks to induce obesity and hyperglycemia, and followed by a nitric oxide synthase inhibitor, for the additional 5 weeks to induce hypertension and MetS. This MetS mouse model caused a mild diastolic and endothelial dysfunction. We observed that, MetS was characterized by decreased levels of free H2S and sulfane-sulfur and downregulation of MPST in the aorta of animals with MetS. Global deletion of Mpst (Mpst-/-) results in increased body weight and greater glucose intolerance in mice with MetS, without affecting their blood pressure. Whole transcriptome analysis in aortic tissue revealed an upregulation of genes involved in the immune response; CD8+ cell infiltration and T-cell activation-related pathways were observed among the most affected biological processes in Mpst-/- mice with MetS.
Project description:The metabolic syndrome (MetS) is attributed to a number of risk factors related to obesity and its comorbidities such as hypertension, increased blood glucose, hypertriglyceridemia and cardiovascular disease (CAD). Several mouse models have been used trying to understand the metabolic abnormalities occur in obesity and MetS. However, The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model better describes the physiology and pathophysiology of the MetS upon high fat diet (HFD) feeding. Towards MetS treatment, Roux-en-Y gastric bypass (RYGB) is a surgical bariatric approach that allows to achieve sustained and long-term weight loss and to improve comorbidities of the MetS. The aim of this study was to elucidate whether improvements in lipid and glucose metabolism after RYGB surgery are body weight-dependent or not and to identify transcriptomic signatures related to these phenotypic observations.
Project description:Evaluate differences in gene methylation levels between obese men with and without the metabolic syndrome Visceral adipose tissue from obese men with the metabolic syndrome (MetS+, N=7) vs. obese men without the metabolic syndrome (MetS-, N=7)
Project description:Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here we show for the first time that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptors alpha (PPARalpha), a master regulator of energy metabolism in myocardium. Mechanistically, NELF helps stablize the transcription initation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARalpha-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes. 3 Nelf-b f/f and 3 Nelf-b f/f; CreER female mice were injected with Tamoxifen at 8 wk old. Heart tissue were harvested at 20 wks old and used for RNA preparation.