Fas (CD95) is a member of the TNF receptor family and its activation has been shown to induce secretion of proinflammatory cytokines. The aim of this study was to investigate the contribution of FAS in adipocytes to the metabolic complications associated with obesity. Results showed that Fas expression was elevated in adipose tissue in both common genetic and nutritional mouse obesity models as well as in obese humans and even more so in obese diabetic patients. Moreover, both total body Fas-deficient and adipocyte-specific Fas-KO mice were significantly protected against adipocyte and whole-body insulin-resistance induced by high-fat diet feeding. It was also observed that Fas activation in adipocytes contributed to the increased production and secretion of inflammatory cytokines in obesity and consequently contributed to the development of insulin resistance. Thus, Fas appears to be an interesting target for the treatment of metabolic complications associated with obesity.
Documentation centre