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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The epigenetic signature of systemic insulin resistance in obese women [SC]

ABSTRACT: Impaired ability of insulin to stimulate cellular glucose uptake and regulate metabolism, that is insulin resistance (IR), links adiposity to metabolic disorders such as type 2 diabetes (T2D), dyslipidemia and cardiovascular disease (Langenberg, 2012). Both genetic and epigenetic factors are implicated in development of systemic IR (Vaag, 2001). IR is characterized by elevated levels of fasting insulin in the general circulation. The aim of this study is to explore whether white adipose tissue (WAT) epigenetic dysregulation is associated with systemic IR by global CpG methylation and gene expression profiling in subcutaneous and visceral adipose tissue. A secondary aim is to determine whether the DNA methylation signature in peripheral blood mononuclear cells reflect WAT methylation, and can be used as marker for systemic IR. DNA methylation was analyzed in DNA extracted from SAT (subcutaneous adipose tissue) and VAT (visceral adipose tissue) pieces, as well as PBMCs (peripheral blood mononuclear cells), using the Infinium Human Methylation 450 BeadChip assay. This data is from SAT.

ORGANISM(S): Homo sapiens

SUBMITTER: Ingrid Dahlman

PROVIDER: E-GEOD-76398 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The epigenetic signature of systemic insulin resistance in obese women [BL]

Project description:Impaired ability of insulin to stimulate cellular glucose uptake and regulate metabolism, that is insulin resistance (IR), links adiposity to metabolic disorders such as type 2 diabetes (T2D), dyslipidemia and cardiovascular disease (Langenberg, 2012). Both genetic and epigenetic factors are implicated in development of systemic IR (Vaag, 2001). IR is characterized by elevated levels of fasting insulin in the general circulation. The aim of this study is to explore whether white adipose tissue (WAT) epigenetic dysregulation is associated with systemic IR by global CpG methylation and gene expression profiling in subcutaneous and visceral adipose tissue. A secondary aim is to determine whether the DNA methylation signature in peripheral blood mononuclear cells reflect WAT methylation, and can be used as marker for systemic IR. DNA methylation was analyzed in DNA extracted from SAT (subcutaneous adipose tissue) and VAT (visceral adipose tissue) pieces, as well as PBMCs (peripheral blood mononuclear cells), using the Infinium Human Methylation 450 BeadChip assay. This data is from PBMCs.

2016-08-01 | E-GEOD-76285 | biostudies-arrayexpress

The epigenetic signature of systemic insulin resistance in obese women [OM]

2016-08-01 | E-GEOD-76394 | biostudies-arrayexpress

The epigenetic signature of systemic insulin resistance in obese women [OM]

2016-08-01 | GSE76394 | GEO

The epigenetic signature of systemic insulin resistance in obese women [BL]

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The epigenetic signature of systemic insulin resistance in obese women [SC]

2016-08-01 | GSE76398 | GEO

Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes (Microarray Expression)

Project description:Accumulation of subcutaneous white adipose tissue (WAT) is associated with increased insulin sensitivity, low levels of inflammation and a generally metabolically-healthy state, whereas accumulation of visceral adipose tissue is associated with insulin resistance, adipose tissue inflammation and metabolic syndrome. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched in subcutaneous WAT that can target degradation of a variety of peptides, including insulin, IL6, and β-amyloids. Here, we show that MME in white preadipocytes is differently expressed in subcutaneous vs visceral WAT, and favors insulin signaling and a low inflammatory response. Thus, knockdown of MME in preadipocytes increases the inflammatory response to substance P and amyloidβ aggregates. This is associated with increased basal insulin signaling and decreased insulin-stimulated signaling. Moreover, MME differentially regulates the internalization and turnover of the α/β subunits of the insulin receptor. Thus, MME is a novel regulator of the insulin receptor in adipose tissue and may serve as a therapeutic target to increase insulin sensitivity and decrease inflammatory susceptibility.

2019-02-25 | GSE117352 | GEO

Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes (RNA-Seq)

2019-02-25 | GSE117270 | GEO

Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes

Project description:Accumulation of visceral white adipose tissue (WAT) associates with insulin resistance, adipose tissue inflammation, and metabolic syndrome, whereas accumulation of subcutaneous WAT may be protective. We aimed to identify molecular mechanisms that might provide mechanistic insights underlying the phenotypic differences in these tissues. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched in subcutaneous WAT that can target degradation of a variety of peptides, including insulin, IL6, and β-amyloids. We hypothesized that MME contributes to adipose depot-specific metabolic properties.

2019-02-25 | GSE117353 | GEO

Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on a high-fat, high-sugar diet.

Project description:Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on the pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-kB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/- resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys.

2014-04-21 | GSE50005 | GEO

Worsening of Obesity and Metabolic Status Yields Similar Molecular Adaptations_Subcutaneous and Visceral Adipose Tissue

Project description:Context: It is not known whether biological differences reported between subcutaneous (SAT) and visceral (VAT) adipose tissue depots underlie the pathogenicity of visceral fat. Objective: We compared SAT and VAT gene expression according to obesity, visceral fat accumulation, insulin resistance and presence of the metabolic syndrome. Design: Subjects were assigned into 4 groups (lean, overweight, obese and obese with metabolic syndrome). Setting: Subjects were recruited at a university hospital. Patients: 32 women were included. Main Outcome Measures: Anthropometric measurements, euglycemic hyperinsulinemic clamps, blood analyses and computed tomography scans were performed and paired samples of SAT and VAT were obtained for DNA microarray-based gene expression profiling.

2010-12-07 | GSE24883 | GEO

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