Fat-Produced Adipsin Regulates Inflammatory Arthritis

Yongjia Li, Wei Zou, Jonathan R. Brestoff, Nidhi Rohatgi, Xiaobo Wu, John P. Atkinson, Charles A. Harris, Steven L. Teitelbaum. Cell Reports, Volume 27, Issue 10, 4 June 2019, Pages 2809-2816.e3 Read More


We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding “fat-free” (FF) mice completely lacking white and brown fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting a predisposition to severe IA. Surprisingly, FF mice are resistant to K/BxN serum-induced IA and attendant bone destruction. Despite robust systemic basal neutrophilia, neutrophil infiltration into joints of FF mice does not occur when challenged with K/BxN serum. Absence of adiponectin, leptin, or both has no effect on joint disease, but deletion of the adipokine adipsin (complement factor D) completely prevents serum-induced IA. Confirming that fat-expressed adipsin modulates the disorder, transplantation of wild-type (WT) adipose tissue into FF mice restores susceptibility to IA, whereas recipients of adipsin-deficient fat remain resistant. Thus, adipose tissue regulates development of IA through a pathway in which adipocytes modify neutrophil responses in distant tissues by producing adipsin. The relationship of fat and inflammatory arthritis (IA) is poorly defined. Li et al. generate fat-free (FF) mice and observe that they are completely resistant to IA because of a lack of adipsin. Their studies provide evidence that fat regulates IA development by adipsin activation of the complement pathway. © 2019 The Author(s)

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Posted on June 10, 2019
Posted in: Neurogenetics & Transcriptomics, Neurovascular Injury & Repair, Publications Authors: ,