Increased basement membrane components in adipose tissue during obesity: Links with TGF- And metabolic phenotypes

Abstract

Context: Collagen accumulation around adipocytes and vessels (ie, pericellular fibrosis) is a hallmark of obese adipose tissue associated with altered metabolism. Objective: Our objective was to evaluate components of basement membrane (BM) in adipose tissue, including collagen IV, a major BM component, and its relationships with metabolic parameters and TGFβ isoforms. Design and Setting: We used immuno-techniques and gene expression approaches to detect BM components in subcutaneous and visceral adipose tissue samples. Adipocytes and endothelial cells were isolated from lean and obese adipose tissue. We also focused on the expression of COL4A1 correlated to metabolic variables in moderate obesity and, in severe obesity before and after bariatric surgery. Using in vitro analysis,weexplored the impact of TGFβ isoforms on the expression of inflammatory and extracellular matrix genes in adipocytes and endothelial cells. Results: BMcomponents were detected around adipocytes and endothelial cells, and were increased in obese adipocytes. COL4A1 expression was positively correlated with insulin-resistance indices in obesesubjectsandshowedlessreductioninseverelyobesesubjectswithpoorerinsulin-resistanceoutcomes 6 months after gastric bypass. COL4A1 expression also correlated with TGFβ1 and TGFβ3 gene expressions in subcutaneous adipose tissue. Stimulating isolated adipocytes and endothelial cells in vitro with these TGFβisoformsshowedaninflammatoryandpro-fibroticphenotype.However,TGFβ1andTGFβ3exposure only provoked COL4A1 overexpression in endothelial cells and not in adipocytes. Conclusion:Thedisorganization of severalBMcomponents, including collagen IV, could contribute to pathological alterations of obese adipose tissue and cells.