Although these animal data reveal a beneficial impact of TRAIL upon adipose tissue homeostasis and suggest a protective effect against obesity which is tightly linked with T2DM, a number of other experimental studies investigating the direct metabolic effects of TRAIL on fat cell biology in vitro provide controversial evidence suggesting a rather obesogenic effect by promoting an insulin-resistant, inflammatory and dysfunctional phenotype of adipose tissue [58,59,60]. This evidence concerns the gene TNFSF10 and type 2 diabetes mellitus.