Deficiency for Costimulatory Receptor 4-1BB Protects Against Obesity-Induced Inflammation and Metabolic Disorders.
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. RESEARCH DESIGN AND 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.[1]References
- Deficiency for Costimulatory Receptor 4-1BB Protects Against Obesity-Induced Inflammation and Metabolic Disorders. Kim, C.S., Kim, J.G., Lee, B.J., Choi, M.S., Choi, H.S., Kawada, T., Lee, K.U., Yu, R. Diabetes (2011) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
