Comment on: Kim et al. Deficiency for Costimulatory Receptor 4-1BB Protects Against Obesity-Induced Inflammation and Metabolic Disorders. Diabetes 2011;60:3159–3168

In the December 2011 issue of Diabetes , Kim et al. (1) reported that 4-1BB (CD137/TNFRSF9) deficiency protected against high-fat diet–induced obesity, glucose intolerance, and fatty liver disease. They found that 4-1BB deficiency reduced number and activation of macrophages/CD8+ T cells/Th1 cells into adipose tissue, reduced circulating proinflammatory cytokines, and improved insulin sensitivity/liver pathology with respect to wild-type (WT) animals fed the same diet. This is an important advance in the field because antagonism of the 4-1BB/4-1BB ligand interaction (e.g., modulating its expression, blocking receptor/ligand interaction, and interfering signaling) could help reduce macrophage infiltration and adipose tissue inflammation in obesity. However, in an …