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Hyperandrogenemia and western-style diet act synergistically on transcription and DNA methylation in visceral adipose tissue of a non-human primate model [RRBS]

ABSTRACT: We have recently developed a nonhuman primate (NHP) model to address the effects of hyperandrogenemia (modestly elevated testosterone; T), a high-fat, obesogenic Western-style diet (WSD), or combined T+WSD. To address the molecular mechanisms underlying adipocyte dysfunction, visceral adipose tissue biopsies were analyzed for whole-genome gene expression and DNA methylation, using RNA-seq and reduced-representation bisulfite sequencing (RRBS), respectively. We show that the combination of T + WSD induces a significantly stronger transcriptional response than T or WSD alone, including regulation of genes whose expression is altered in adipose tissue of PCOS women. Gene expression patterns indicate alterations in cAMP, LXR/RXR, HIPPO, Wnt signaling and eicosanoid and retinol biosynthesis pathways. Analysis of DNA methylation shows that genes from the cAMP signaling pathway are also differentially methylated in T +WSD, which also globally resulted in a greater number of differentially methylated regions (DMRs) than T or WSD alone. Collectively, our results show that hyperandrogenemia and WSD exhibit synergistic effects on the visceral adipose tissue transcriptome and methylome, resulting in activation of biological processes that may contribute to the adipose tissue dysfunction characteristic of PCOS.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE124708 | GEO | 2019/01/07

REPOSITORIES: GEO

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Hyperandrogenemia and western-style diet act synergistically on transcription and DNA methylation in visceral adipose tissue of a non-human primate model [RNA-Seq]

Project description:We have recently developed a nonhuman primate (NHP) model to address the effects of hyperandrogenemia (modestly elevated testosterone; T), a high-fat, obesogenic Western-style diet (WSD), or combined T+WSD. To address the molecular mechanisms underlying adipocyte dysfunction, visceral adipose tissue biopsies were analyzed for whole-genome gene expression and DNA methylation, using RNA-seq and reduced-representation bisulfite sequencing (RRBS), respectively. We show that the combination of T + WSD induces a significantly stronger transcriptional response than T or WSD alone, including regulation of genes whose expression is altered in adipose tissue of PCOS women. Gene expression patterns indicate alterations in cAMP, LXR/RXR, HIPPO, Wnt signaling and eicosanoid and retinol biosynthesis pathways. Analysis of DNA methylation shows that genes from the cAMP signaling pathway are also differentially methylated in T +WSD, which also globally resulted in a greater number of differentially methylated regions (DMRs) than T or WSD alone. Collectively, our results show that hyperandrogenemia and WSD exhibit synergistic effects on the visceral adipose tissue transcriptome and methylome, resulting in activation of biological processes that may contribute to the adipose tissue dysfunction characteristic of PCOS.

2019-01-07 | GSE124707 | GEO

Gene Expression Data of Adipose Stem Cells from Normal-Weight Polycystic Ovary Syndrome Women vs. Controls

Project description:In vitro studies of subcutaneous (SC) abdominal adipose stem cells (ASC) from women with polycystic ovary syndrome (PCOS) show altered ASC commitment to preadipocytes and differentiation to mature adipocytes related to hyperandrogenism. The goal of the study is to use microarrays to examine whether SC abdominal ASC gene expression are altered in normal-weight PCOS women and correlated with hyperandrogenemia and/or insulin resistance, which are prevalent clinical pathologies of PCOS.

2019-01-24 | GSE124226 | GEO

Transcription profiling of human omental adipose tissue in women with polycystic ovary syndrome (PCOS)

Project description:CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of the syndrome. OBJECTIVE: The objective was to study the expression profiles of omental fat biopsy samples obtained from morbidly obese women with or without PCOS at the time of bariatric surgery. DESIGN: This was a case-control study. SETTINGS: We conducted the study in an academic hospital. PATIENTS: Eight PCOS patients and seven nonhyperandrogenic women submitted to bariatric surgery because of morbid obesity. INTERVENTIONS: Biopsy samples of omental fat were obtained during bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was high-density oligonucleotide arrays. RESULTS: After statistical analysis, we identified changes in the expression patterns of 63 genes between PCOS and control samples. Gene classification was assessed through data mining of Gene Ontology annotations and cluster analysis of dysregulated genes between both groups. These methods highlighted abnormal expression of genes encoding certain components of several biological pathways related to insulin signaling and Wnt signaling, oxidative stress, inflammation, immune function, and lipid metabolism, as well as other genes previously related to PCOS or to the metabolic syndrome. CONCLUSION: The differences in the gene expression profiles in visceral adipose tissue of PCOS patients compared with nonhyperandrogenic women involve multiple genes related to several biological pathways, suggesting that the involvement of abdominal obesity in the pathogenesis of PCOS is more ample than previously thought and is not restricted to the induction of insulin resistance.

2007-10-26 | E-GEOD-5090 | biostudies-arrayexpress

Chronically elevated androgen and/or consumption of a Western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle.

Project description:Purpose: To investigate the impact of chronically-elevated androgens in presence and absence of an obesogenic diet on oocyte quality in the naturally-selected primate periovulatory follicle. Methods: Rhesus macaques were treated using a 2-by-2 factorial design (n=10/treatment) near onset of menarche with implants containing either cholesterol (C) or testosterone (T; 4-5 fold increase above C) and a standard or “Western-style” diet alone (WSD), or in combination (T+WSD). Following ~3.5 years of treatment, females underwent controlled ovulation (COv; n=7-10/treatment) cycles, and contents of the naturally-selected periovulatory follicle were aspirated. Follicular fluid (FF) was analyzed for cytokines, chemokines, growth factors, and steroids. RNA was extracted from luteinizing granulosa cells (LGCs) and assessed by RNA-seq. Results: Only healthy, metaphase (M) I/II-stage oocytes (100%) were retrieved in the C group, whereas degenerated oocytes were prevalent in other groups (33-43%; overall effect of WSD and T, p=0.1). Levels of two chemokines and one growth factor were reduced (p<0.04) in FF of follicles with a MI/MII oocyte in WSD+T (CCL11) or T and WSD+T groups (CCL2 and FGF2) compared to C and/or WSD. Intrafollicular cortisol was elevated in T compared to C follicles (p<0.02). Changes in expression pattern of 640+ gene products were detected in LGC samples from follicles with degenerated oocytes versus MI/MII-stage oocytes. Pathway analysis on RNAs altered by T and/or WSD found enrichment of genes mapping to steroidogenic and immune cell pathways. Conclusions: Female primates experiencing hyperandrogenemia and/or consuming a WSD exhibit an altered intrafollicular microenvironment and reduced oocyte quality/competency, despite displaying menstrual cyclicity.

2019-09-05 | GSE128569 | GEO

Transcription profiling of mouse adipocytes and white adipose tissue of mice maintained on normal chow or high fat diet

Project description:We studied the role of the cAMP responsive factor CREB in promoting insulin resistance following its activation in adipose under obese conditions; We identified genes that were upregulated in primary cultures of mouse adipocytes following exposure to forskolin; and we characterized genes that are also induced in white adipose tissue in mice maintained on a high fat diet. Experiment Overall Design: Primary cultures of mouse adipocytes,harvested from visceral adipose tissue, were exposed to forskolin (10uM) or vehicle control (DMSO) for 2 hours. White adipose tissue (epididymal fat pads) were collected from mice maintained on a 60% high fat diet for 12 weeks and from control mice on normal chow.

2009-03-07 | E-GEOD-14363 | biostudies-arrayexpress

Proteomic changes in adipose tissue and skeletal muscle in women with PCOS

Project description:Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including abdominal obesity, dyslipidemia and an increased risk of developing type 2 diabetes. Despite the high prevalence of >15%, the pathophysiology of the syndrome is unclear. Gene expression array data from skeletal muscle and adipose tissue have provided some information about dysregulated metabolic pathways in women with PCOS, but the transcriptomic data need to be verified by proteomics to advance our understanding of PCOS. Skeletal muscle and adipose tissue biopsies from 10 women with PCOS and 10 controls were subjected to global proteomic analysis. Protein expression differences between cases and controls were based on Student’s t-test and corrected for multiple testing. In total, we identified 5000 proteins in adipose tissue and 3480 proteins in skeletal muscle. After correction for multiple testing, 74 proteins with q < 0.05 corresponding to 72 unique proteins were found to be differentially expressed in adipose tissue from women with PCOS versus controls. And, 123 proteins with q < 0.05 corresponding to 120 unique proteins were found to be differentially expressed in skeletal muscle from women with PCOS versus control. We then applied pathway analysis to the total protein and phosphopeptide data using PRISM and Enrichr.

2024-01-09 | PXD025358 | Pride

miRNA expression data from lean PCOS adipose vs BMI matched control women

Project description:Why ~70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR), above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT), remains a fundamental question. In these experiments, we sought to explore the role of miRNAs in the AT of PCOS and matched controls. Analysis determined that PCOS AT has a differentially expressed miRNA profile, including upregulated miR-93. We observed a significant association between HOMA-IR, and GLUT4 and miR-93 expression in human AT. Our results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93, and demonstrate upregulated miR-93 expression in PCOS, possibly accounting for the IR of the syndrome, and also in non-PCOS women with IR. We performed miRNA microarrays to determine PCOS-related miRNA expression in adipose derived from lean PCOS patients and matched control women. We analyized miRNA from total RNA extracted from subcutaneous (sc) adipose tissue from three lean PCOS patients and three matched control women.

2012-09-06 | E-GEOD-37914 | biostudies-arrayexpress

Coding and Non-coding gene expression signatures of endometrium from Polycystic Ovary Syndrome Patients

Project description:Polycystic ovary syndrome (PCOS), one of the most common endocrinal diseases among reproductive-aged women, is characterized by hyperandrogenemia, chronic oligo/anovulation and polycystic ovarian morphology. In this research, we presented microarrays to identify the differential expressed protein-coding genes and lncRNAs expression profile in the endometrium during the window of implantation between the PCOS and healthy subjects.

2019-09-13 | GSE137354 | GEO

Coding and Non-coding gene expression signatures of granulosa cells from Polycystic Ovary Syndrome Patients

Project description:Polycystic ovary syndrome (PCOS), one of the most common endocrinal diseases among reproductive-aged women,is characterized by hyperandrogenemia, chronic oligo/anovulation and polycystic ovarian morphology. In this research, we presented microarrays to identify the differential expressed protein-coding genes and lncRNAs expression profile in the luteinized granulosa cells obtained from PCOS and healthy control patients.

2018-10-30 | GSE114419 | GEO

Expression data from mice epididymal adipose tissue

Project description:Visceral white adipose tissue is closed correlated with obesity and metabolic dysfunction. Epididymal adipose tissue (eWAT) is considered as typical visceral white adipose tissue. Induction of browning of white adipose tissue improves metabolic dysfunction such as insulin resistance. In contrast to mice subcutaneous adipose tissue, visceral fat do not show significant browning under 4°C. However,under physiologically tolerable low temperature visceral adipose tissue can turn brown. We used microarrays to detail the global programme of gene expression in C57Bl/6 mice epididymal adipose tissue exposed to thermoneutral 30°C, 4°C and temperatures lower than 4°C.

2017-06-12 | GSE74062 | GEO

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