Expression Of Visceral Adipose Tissue Extracellular Matrix Related Genes Correlates With Insulin Resistance And Predicts Metabolic Improvement Following Bariatric Surgery

Abstract

Background: The role of different adipose tissues (AT) regarding alterations in extracellular matrix (ECM) remodeling in obesity is currently unknown. Objective: To perform a comparative analysis on the expression of ECM-related genes in four tissues of interest between obese and non-obese patients. Methods: A comparative transcriptional analysis was performed using microarrays to analyze the expression of ECM-related genes in subcutaneous AT, omentum, mesentery and peritoneum between obese (n=30) and non-obese (n=13) individuals. The main expression differences were validated by RT-qPCR, and their relationship with different clinical variables and evolution following bariatric surgery (BS) was analyzed. Results: Microarray analysis showed overexpression of ECM-related genes in visceral tissues of obese patients, while expression differences between groups were scarce in subcutaneous AT. Omental and mesenteric expression of HAS1, ADAMTS4, THBS1 and S100A8 were associated with obesity and insulin resistance. Mesenteric overexpression of ADAMTS family metallopeptidases was also detected in insulin-resistant individuals. Epiploic expression of HAS1, THBS1, VCAN and S100A8, as well as peritoneal expression of THBS1, ADAMTS1 and -4 correlated with HOMA-IR in the studied subjects. After BS, omental THBS1 expression and mesenteric ADAMTS9 expression showed correlation with HOMA-IR variation 12 months following surgery. Conclusions: Our results point to a relationship between the over-expression of ECM-related genes in the analyzed visceral tissues and insulin resistance, as well as with metabolic improvement after BS. Our study highlights the possible contribution of mesenteric AT as well as mesothelial cells to metabolic dysregulation in the obese patient.