| First Author | van Dam AD | Year | 2017 |
| Journal | Int J Obes (Lond) | PubMed ID | 28852207 |
| Mgi Jnum | J:251750 | Mgi Id | MGI:6093752 |
| Doi | 10.1038/ijo.2017.209 | Citation | van Dam AD, et al. (2018) IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcgamma-receptor or complement. Int J Obes (Lond) 42(2):260-269 |
| abstractText | BACKGROUND/OBJECTIVES: In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcgamma receptors (FcgammaR) and by activating the complement system. The aim of our study was to investigate whether activation of FcgammaR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance. METHODS: We studied mice lacking all four FcgammaRs (FcgammaRI/II/III/IV(-/-)), only the inhibitory FcgammaRIIb (FcgammaRIIb(-/-)), only the central component of the complement system C3 (C3(-/-)), and mice lacking both FcgammaRs and C3 (FcgammaRI/II/III/IV/C3(-/-)). All mouse models and wild-type controls were fed a high-fat diet (HFD) for 15 weeks to induce obesity. Glucose metabolism was assessed and adipose tissue was characterized for inflammation and adipocyte functionality. RESULTS: In obese WAT of wild-type mice, B cells (+142%, P<0.01) and IgG (+128% P<0.01) were increased compared to lean WAT. Macrophages of FcgammaRI/II/III/IV(-/-)mice released lower levels of cytokines compared to wild-type mice upon IgG stimulation. Only C3(-/-) mice showed reduced HFD-induced weight gain as compared to controls (-18%, P<0.01). Surprisingly, FcgammaRI/II/III/IV(-/-) mice had deteriorated glucose tolerance (AUC +125%, P<0.001) despite reduced leukocyte number (-30%, P<0.05) in gonadal WAT (gWAT), whereas glucose tolerance and leukocytes within gWAT in the other models were unaffected compared to controls. Although IgG in gWAT was increased (+44 to +174%, P<0.05) in all mouse models lacking FcgammaRIIb, only FcgammaRI/II/III/IV/C3(-/-) mice exhibited appreciable alterations in immune cells in gWAT, for example, increased macrophages (+36%, P<0.001). CONCLUSIONS: Lack of FcgammaRs reduces the activity of macrophages upon IgG stimulation, but neither FcgammaR nor C3 deficiency protects against HFD-induced glucose intolerance or reduces adipose tissue inflammation. This indicates that if obesity-induced IgG contributes to the development of glucose intolerance, this is not mediated by FcgammaR or complement activation. |
