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Relationship between insulin sensitivity and gene expression in human skeletal muscle

ABSTRACT: The aim of this study was therefore to investigate molecular mechanisms associated with insulin sensitivity in skeletal muscle by relating global skeletal muscle gene expression with a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR). To identify genes with skeletal muscle expression related to insulin sensitivity, we obtained muscle biopsies from 38 non-diabetic participants in study A. We then profiled muscle gene expression using Affymetrix oligonucleotide microarrays (Affymetrix Custom Array NuGO-Hs1a520180 GeneChip). To replicate the findings from study A, we included 9 non-diabetic participants from study B. We performed skeletal muscle gene expression profiling from these participants using the Agilent oligonucleotide microarrays (Agilent-G4112F (Feature Number version)). Insulin sensitivity was estimated using the 1/HOMA-IR method calculated from the oral glucose tolerance test (OGTT) values. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161721 | GEO | 2020/11/19

REPOSITORIES: GEO

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Project description:The obese, insulin resistant state is characterized by impairments in lipid metabolism. Dietary polyphenols might improve these deteriorations. We have previously shown that 3-days supplementation of combined Epigallocatechin-gallate and Resveratrol (E+R) increased energy expenditure, which was accompanied by improved metabolic flexibility after a high-fat mixed-meal (HFMM) in men. The present study aimed to investigate whether these short-term effects translate into longer-term improvement of insulin sensitivity and lipid metabolism. In this randomized, double-blind study, 42 overweight subjects (21 male, 38Â±2 yrs, BMI 29.7Â±0.5 kg/m2, HOMA-IR 2.1Â±0.2) received either E+R (300 and 80 mg/d, respectively) or placebo (PLA) for 12 weeks (3 months). Before (t0) and after (t3) intervention, tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with stable isotope infusion. Fasting and postprandial (HFMM) lipid metabolism was assessed using indirect calorimetry and blood sampling. Adipose tissue and skeletal muscle lipolysis was measured using microdialysis in men and skeletal muscle biopsies were collected to assess mitochondrial function and gene expression alterations via microarray analysis. E+R supplementation increased fasting (P=0.06) and postprandial (P=0.03) fat oxidation but did not alter energy expenditure compared to PLA. This was accompanied by an E+R-induced increase in oxidative capacity in permeabilized muscle fibers (p<0.05). Moreover, E+R supplementation attenuated the increase in plasma triacylglycerol concentration that was observed in the PLA group (AUC, p<0.05), and tended to decrease visceral fat mass (P=0.09). Finally, insulin-stimulated glucose disposal and suppression of endogenous glucose production were not affected by E+R supplementation. 12 weeks E+R supplementation increased whole-body fat oxidation and skeletal muscle oxidative capacity, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. To identify pathways that may underlie the E+R-induced improvement of skeletal muscle mitochondrial capacity, we performed microarray analysis on skeletal muscle biopsies (vastus lateralis muscle), collected before and after 12-weeks E+R or PLA treatment. Gene Set Enrichment Analysis (GSEA) indicated that the most upregulated pathways after E+R supplementation were related to the citric acid cycle and respiratory electron transport chain, while pathways related to carbohydrate metabolism were upregulated in the PLA group. In this randomized, double-blind placebo-controlled, parallel intervention trial, subjects received either a combination of E+R supplements (INTV, 282 mg/d and 80 mg/d, respectively) or placebo (PLA, partly hydrolyzed microcrystalline cellulose-filled capsules) for a period of 12 weeks (3 months) to assess effects of E+R supplementation on tissue-specific insulin sensitivity (primary outcomes) and fasting and postprandial substrate metabolism (secondary outcomes). Skeletal muscle (m. vastus lateralis) biopsies were taken under local anesthesia during fasting conditions before (t0) and after the 12-weeks (t3) intervention period. Extraxted RNA was hybridized on HTA 2.0 Affymetrix arrays and microarray analysis was performed on paired sample sets for 27 subjects (p, PLA n = 14; E+R n = 13).

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Relationship between insulin sensitivity and gene expression in human skeletal muscle

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