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

  1. Dario C. Ramirez
  1. From the Laboratory of Experimental and Therapeutic Medicine, Multidisciplinary Institute for Biological Investigations of San Luis, San Luis, Argentina, and the Department of Molecular Biology, National University of San Luis, San Luis, Argentina
  1. Corresponding author: Dario C. Ramirez, ramirezlabimibiosl{at}

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 …

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