The immune signaling molecule 4-1BB stimulation reduces adiposity, insulin resistance, and hepatosteatosis in obese mice

Endocrinology. 2010 Oct;151(10):4725-35. doi: 10.1210/en.2010-0346. Epub 2010 Aug 18.


Immune cells (e.g. macrophages and T cells) in adipose tissue play a crucial role in the development of obesity-induced inflammation and metabolic disorders. Here we report findings suggesting that the immune signaling molecule 4-1BB/CD137 is a novel target for treatment of obesity and metabolic disorders. 4-1BB stimulation with agonistic antibody reduced body weight and adiposity and markedly improved glucose intolerance and hepatosteatosis in diet-induced obese mice and genetically obese/diabetic mice. Increases in lymphoid T cell expansion/activation and adipose/hepatic CD8+ T cell recruitment were evident in the anti-4-1BB antibody-treated obese mice. Glycolysis, β-oxidation, and oxygen consumption rates also increased in the treated mice. These findings suggest that 4-1BB-stimulation accompanied by CD8+ T cell expansion/activation enhances glucose/lipid metabolism, leading to increased energy expenditure. Manipulation of 4-1BB may provide a unique immunological strategy against obesity and metabolic disorders.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand / agonists*
  • 4-1BB Ligand / immunology*
  • 4-1BB Ligand / physiology
  • Adiposity / drug effects*
  • Adiposity / immunology
  • Animals
  • Antibodies / pharmacology*
  • Antibodies / therapeutic use
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Fatty Liver / complications
  • Fatty Liver / prevention & control*
  • Glucose Intolerance / immunology
  • Glucose Intolerance / prevention & control
  • Immunotherapy
  • Insulin Resistance* / immunology
  • Lymphocyte Activation / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / complications
  • Obesity / immunology
  • Obesity / metabolism
  • Obesity / therapy*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology


  • 4-1BB Ligand
  • Antibodies