TY - JOUR
T1 - Fat-Produced Adipsin Regulates Inflammatory Arthritis
AU - Li, Yongjia
AU - Zou, Wei
AU - Brestoff, Jonathan R.
AU - Rohatgi, Nidhi
AU - Wu, Xiaobo
AU - Atkinson, John P.
AU - Harris, Charles A.
AU - Teitelbaum, Steven L.
N1 - Funding Information:
This work was supported by Shriners Hospitals for Children grant 85400-STL (to S.L.T.); NIH grants R37 AR046523, R01 DK111389, and P30 AR057235 (to S.L.T.), R01 DK106083 (to C.A.H.), and P30 AR073752 and R01 GM099111 (to J.P.A. and X.W.); and The Children's Discovery Institute grant MI-F-2019-795 (to J.R.B.). Y.L. designed and performed experiments and wrote the manuscript. W.Z. and J.R.B. designed and performed experiments and edited the manuscript. N.R. designed experiments. X.W. J.P.A. and C.A.H. designed experiments and edited the manuscript. S.L.T. designed experiments and wrote the manuscript. The authors declare no competing interests.
Funding Information:
This work was supported by Shriners Hospitals for Children grant 85400-STL (to S.L.T.); NIH grants R37 AR046523 , R01 DK111389 , and P30 AR057235 (to S.L.T.), R01 DK106083 (to C.A.H.), and P30 AR073752 and R01 GM099111 (to J.P.A. and X.W.); and The Children’s Discovery Institute grant MI-F-2019-795 (to J.R.B.).
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/6/4
Y1 - 2019/6/4
N2 - 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.
AB - 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.
KW - adipsin
KW - inflammatory arthritis
KW - neutrophils
UR - http://www.scopus.com/inward/record.url?scp=85066273830&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.05.032
DO - 10.1016/j.celrep.2019.05.032
M3 - Article
C2 - 31167128
AN - SCOPUS:85066273830
SN - 2211-1247
VL - 27
SP - 2809-2816.e3
JO - Cell Reports
JF - Cell Reports
IS - 10
ER -