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J Biol Chem. 2017 Apr 21;292(16):6569-6582. doi: 10.1074/jbc.M115.712646. Epub 2017 Mar 3.

Adiponectin confers protection from acute colitis and restricts a B cell immune response.

Author information

1
From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
2
the Department of Molecular and Cell Biology and.
3
the University of Melbourne, Victoria, VIC 3010, Australia, and.
4
From the Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia, lionel.hebbard@jcu.edu.au.
5
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD 4811, Australia.

Abstract

Adiponectin demonstrates beneficial effects in various metabolic diseases, including diabetes, and in bowel cancer. Recent data also suggest a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin knock-out mice were orally administered dextran sulfate sodium for 7 days and were compared with wild-type mice. The severity of disease was analyzed histopathologically and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyze the in vitro effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin knock-out mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration, and an increased presence of activated B cells compared with controls. This was accompanied by an exaggerated proinflammatory cytokine profile and increased STAT3 signaling. Adiponectin knock-out mouse colons had markedly reduced proliferation and increased epithelial apoptosis and cellular stress. In vitro, adiponectin reduced apoptotic, anti-proliferative, and stress signals and restored STAT3 signaling. Following the abrogation of AdipoR1 in vitro, these protective effects of adiponectin were abolished. In summary, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.

KEYWORDS:

STAT3; adiponectin; autoimmunity; colitis; obesity

PMID:
28258220
PMCID:
PMC5399108
DOI:
10.1074/jbc.M115.712646
[Indexed for MEDLINE]
Free PMC Article

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