Expression of anti-angiogenic genes in subcutaneous adipose tissue of the obese individuals with pre-diabetes and type 2 diabetes

Accumulating evidence raises the hypothesis that dysregulation of different intrinsic mechanisms which control most metabolic processes are involved in the development of obesity, metabolic syndrome and type 2 diabetes mellitus, the most profound public health problems. Angiogenesis is an important component of different proliferative processes, in particular, fat tissue growth. Moreover, dysregulation of molecular components of the angiogenesis system can contributes to the development of diabetic complications. We have studied the expression levels of genes related to regulation of angiogenesis (TIMP1, TIMP2, TIMP3, TIMP4, THBS1, THBS2, THBS3, ADAMTS5, LUM, DCN, IL6 and ZEB1) in subcutaneous adipose tissue of obese individuals as well as obese patients with impaired glucose tolerance (prediabetic) and type 2 diabetes using real-time quantitative PCR. We have shown that the expression level of most of these genes with anti-angiogenic properties significantly increases in subcutaneous adipose tissue of obese individuals versus lean patients, being more intense for TIMP1, TIMP2, THBS2 and LUM genes. Increased expression level of TIMP1, TIMP2, TIMP3, ADAMTS5 as well as THBS1 and THBS2 in adipose tissue was found in obese patients with impaired glucose tolerance. At the same time, expression of genes which encode for TIMP1 and TIMP2 strongly decreased in adipose tissue of obese individuals with type 2 diabetes versus subjects with glucose intolerance. Results of this study provide strong evidence that expression of genes mostly related to suppression of angiogenesis is dysregulated in adipose tissue of obese individuals as well as in obese patients with glucose intolerance and type 2 diabetes. It is possible that these changes in the expression of TIMP and THBS genes in adipose tissue in obesity as well as in obese individuals with impaired glucose tolerance and type 2 diabetes can contribute to fat tissue storage, insulin resistance and the development of diabetic complications.