title: Deficiency for costimulatory receptor 4-1BB protects against obesity-induced inflammation and metabolic disorders.
abstract: OBJECTIVE
  Inflammation is an important factor in the development of insulin resistance, type 2 diabetes, and fatty liver disease. As a member of the tumor necrosis factor receptor superfamily (TNFRSF9) expressed on immune cells, 4-1BB/CD137 provides a bidirectional inflammatory signal through binding to its ligand 4-1BBL. Both 4-1BB and 4-1BBL have been shown to play an important role in the pathogenesis of various inflammatory diseases.
  
  
  METHODS
  Eight-week-old male 4-1BB-deficient and wild-type (WT) mice were fed a high-fat diet (HFD) or a regular diet for 9 weeks.
  
  
  RESULTS
  We demonstrate that 4-1BB deficiency protects against HFD-induced obesity, glucose intolerance, and fatty liver disease. The 4-1BB-deficient mice fed an HFD showed less body weight gain, adiposity, adipose infiltration of macrophages/T cells, and tissue levels of inflammatory cytokines (e.g., TNF-α, interleukin-6, and monocyte chemoattractant protein-1 [MCP-1]) compared with HFD-fed control mice. HFD-induced glucose intolerance/insulin resistance and fatty liver were also markedly attenuated in the 4-1BB-deficient mice.
  
  
  CONCLUSIONS
  These findings suggest that 4-1BB and 4-1BBL may be useful therapeutic targets for combating obesity-induced inflammation and metabolic disorders.
authors: Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
authors: Chu-Sook
authors: CS
authors: Kim
authors: Jae Geun
authors: JG
authors: Kim
authors: Byung-Ju
authors: BJ
authors: Lee
authors: Myung-Sook
authors: MS
authors: Choi
authors: Hye-Sun
authors: HS
authors: Choi
authors: Teruo
authors: T
authors: Kawada
authors: Ki-Up
authors: KU
authors: Lee
authors: Rina
authors: R
authors: Yu
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002153:Calorimetry, Indirect; D018932:Chemokine CCL2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005434:Flow Cytometry; D018149:Glucose Intolerance; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000172:deficiency* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053330:4-1BB Ligand; D018932:Chemokine CCL2; D015850:Interleukin-6; D016328:NF-kappa B; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha