Endocrine Abstracts

Background: Chemerin is a recently identified adipocyte-secreted signalling molecule (adipokine) that regulates adipocyte differentiation, metabolism, and inflammation through activation of the cognate receptor Chemokine-Like Receptor 1 (CMKLR1). Circulating chemerin levels are increased in obese patients as well as in patients with inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis. Increased white adipose tissue mass (WAT) and resultant changes in the secretion of several adipokines have been shown to negatively impact the severity and treatment of IBD. Therefore, we hypothesized that chemerin/CMKLR1 signalling represents a novel link between obesity and IBD.

Objectives: To determine whether modulation of chemerin/CMKLR1 signalling impacts weight loss, clinical illness, and colonic inflammation associated with the onset of dextran sodium sulfate (DSS)-induced colitis in mice.

Results: Chemerin and CMKLR1 expression increased in the cecum and distal colon, while CMKLR1 expression decreased in WAT, of DSS-treated mice. Following DSS treatment, WT mice had significantly higher chemerin levels both in the colon and circulation. Moreover, injection of bioactive chemerin into WT mice resulted in greater weight loss and colon inflammation compared to vehicle control. Consistent with this, CMKLR1 knockout mice exhibited decreased early weight loss and a slower onset of clinical illness compared to WT controls. However, CMKLR1-null mice exhibited similar levels of colonic inflammation and clinical illness compared to WT littermates at the final endpoint.

Conclusions: Increased levels of circulating chemerin exacerbated the severity of DSS-induced colitis and CMKLR1-null mice had a delayed onset of colitis. This suggests that chemerin/CMKLR1 signalling modulates the development of IBD.

Disclosure: This work was supported by the Canadian Institutes of Health Research (CIHR).