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

AbstractBackground: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 ofHAS1,ADAMTS4,THBS1andS100A8were associated with obesity and insulin resistance. Mesenteric overexpression ofADAMTSfamily metallopeptidases was also detected in insulin-resistant individuals. Epiploic expression ofHAS1,THBS1,VCANandS100A8, as well as peritoneal expression ofTHBS1,ADAMTS1and-4correlated with HOMA-IR in the studied subjects. After BS, omentalTHBS1expression and mesentericADAMTS9expression 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.