The immune signaling molecule 4-1BB stimulation reduces adiposity, insulin resistance, and hepatosteatosis in obese mice.
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.
Kim
Chu-Sook
CS
Department of Food Science and Nutrition, University of Ulsan, Mugeo-dong, Nam-ku, Ulsan 680-749, South Korea.
Tu
Thai Hien
TH
Kawada
Teruo
T
Kim
Byung-Sam
BS
Yu
Rina
R
D053330:4-1BB Ligand / Q000819:agonists* / Q000276:immunology* / Q000502:physiology; D050154:Adiposity / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005234:Fatty Liver / Q000150:complications / Q000517:prevention & control*; D018149:Glucose Intolerance / Q000276:immunology / Q000517:prevention & control; D007167:Immunotherapy; D007333:Insulin Resistance / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D053330:4-1BB Ligand; D000906:Antibodies