Glucose tolerance in obese men is associated with dysregulation of some angiogenesis-related gene expressions in subcutaneous adipose tissue.

Abstract

Obesity and its metabolic complications are one of the most profound public health problems and result from interactions between genes and environmental. The development of obesity is tightly connected with dysregulation of intrinsic gene expression mechanisms controlling majority of metabolic processes, which are essential for regulation many physiological functions, including insulin sensitivity, cellular proliferation and angiogenesis. Our objective was to evaluate if expression of angiogenesis related genes VEGF-A, CYR61, PDGFC, FGF1, FGF2, FGFR2, FGFRL1, E2F8, BAI2, HIF1A, and EPAS1 at mRNA level in adipose tissue could participate in the development of obesity and metabolic complications. We have shown that expression level of VEGF-A, PDGFC, FGF2, and FGFRL1 genes is decreased in adipose tissue of obese men with normal glucose tolerance (NGT) versus a group of control subjects. At the same time, in this group of obese individuals a significant up-regulation of CYR61, FGF1, FGFR2, E2F8, BAI2, and HIF1A gene expressions was observed. Impaired glucose tolerance (IGT) in obese patients associates with down-regulation of CYR61 and FGFR2 mRNA and up-regulations of E2F8, FGF1, FGF2, VEGF-A and its splice variant 189 mRNA expressions in adipose tissue versus obese (NGT) individuals. Thus, our data demonstrate that the expression of almost all studied genes is affected in subcutaneous adipose tissue of obese individuals with NGT and that glucose intolerance is associated with gene-specific changes in the expression of E2F8, FGF1, FGF2, VEGF-A, CYR61 and FGFR2 mRNAs. The data presented here provides evidence that VEGF-A, CYR61, PDGFC, FGF1, FGF2, FGFR2, FGFRL1, E2F8, BAI2, and HIF1A genes are possibly involved in the development of obesity and its complications.