This study provides the first evidence that the secretome from EAT promotes myocardial fibrosis through the secretion of adipo-fibrokines such as Activin A.

Background/Objectives:The unresolved chronic inflammation of white adipose tissue (WAT) in obesity leads to interstitial deposition of fibrogenic proteins as reparative process. The contribution of omental adipose tissue (oWAT) fibrosis to obesity-related complications remains controversial. The aim of our study was to investigate whether oWAT fibrosis may be related to insulin resistance in severely obese population.Subjects/Methods:Forty obese subjects were studied by glucose clamp before undergoing bariatric surgery and thus stratified according to insulin resistance severity (M-value). From the first (Group B: n=13; M=1.9±0.7 mg kg−1 min−1) and the highest (Group A: n=14; M=4.5±1.4 mg kg−1 min−1) M-value tertiles, which were age-, waist- and body mass index-matched, oWAT samples were then obtained.Gene expression of collagen type I, III and VI, interleukin-6, profibrotic mediators (transforming growth factor (TGF)-β1, activin A, connective tissue growth factor), hypoxia inducible factor-1α (HIF-1α) and macrophage (CD68, monocyte chemotactic protein (MCP)-1, CD86, CD206, CD150) markers were analyzed by quantitative reverse transcription PCR. Adipocyte size and total fibrosis were assessed by histomorphometry techniques.Results:Fibrosis at morphological level resulted significantly greater in Group B compared with Group A, although collagens gene expression did not differ. Notably, collagen VI messenger RNA significantly correlated with collagen I, collagen III, HIF-1α, TGF-β1, CD68, MCP-1 and CD86 transcription levels, supporting their relation with fibrosis development.Conclusions:In conclusion, we show for the first time that human oWAT fibrosis in severe obesity is consistent with a higher degree of insulin resistance measured by glucose clamp. Therefore, collagen deposition could represent a maladaptive mechanism contributing to obesity-related metabolic complications.