Obeid S, Wankell M, Charrez B et al.
Storr Liver Centre, Australia.
The Journal of biological chemistry. Mar 2017.
Adiponectin demonstrates beneficial effects in various metabolic diseases including diabetes, and in bowel cancer. Recent data also suggests 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-knockout mice were orally administered dextran sulfate sodium for 7 days, and were compared to wild-type mice. The severity of disease was analysed histopathologically, and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyse the in vitro effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin-knockout mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration and an increased presence of activated B cells compared to controls. This was accompanied by an exaggerated pro-inflammatory cytokine profile and increased STAT3 signalling. Adiponectin-knockout 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 signalling. Following the abrogation of AdipoR1 in vitro, these protective effects of adiponectin were abolished. In sum, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.