Fas and FasL Expression in Human Adipose Tissue Is Related to Obesity, Insulin Resistance, and Type 2 Diabetes

Context: Deletion of the death receptor Fas (CD95) in adipocytes of mice is associated with improved insulin sensitivity and reduced adipose tissue (AT) inflammation. Objective: Here we investigate the relationship of AT Fas with human obesity. Design and Methods: In paired samples of omental and sc AT from 256 lean and obese (including insulin-sensitive and insulin-resistant subgroups; n = 60) participants, we investigated whether Fas and Fas-ligand (FasL) mRNA expression is fat depot-specific, altered in obesity, and related to measures of AT inflammation and insulin sensitivity. In addition, AT Fas mRNA expression was measured in 16 obese patients after significant weight loss of 45 ± 6.3 kg in the context of a two-step bariatric surgery strategy. Results: Fas and FasL are significantly higher expressed in omental (OM) compared to sc AT. Fas expression correlates with body mass index (OM, r2 = 0.44; sc, r2 = 0.14), AT macrophage infiltration (OM, r2 = 0.36; sc, r2 = 0.16), and glucose infusion rate in ...