Abstract

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.

Original languageEnglish
Pages (from-to)2809-2816.e3
JournalCell Reports
Volume27
Issue number10
DOIs
StatePublished - Jun 4 2019

Keywords

  • adipsin
  • inflammatory arthritis
  • neutrophils

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