TNFα enhances the expression and secretion of chemerin from adipocytes

Abstract

We recently identified a novel adipokine, chemerin that regulates adipogenesis and adipose metabolism via the chemokine‐like receptor 1 (CMKLR1). In humans, serum chemerin levels modestly correlate with measures of body fat and markers of metabolic syndrome suggesting a potential role for chemerin in obesity related diseases. The object of our study was to examine the regulation of chemerin secretion in models of obesity and inflammation. In 12 to 14‐week‐old ob/ob obese mice, serum chemerin levels but not adipocyte expression of chemerin were elevated 2‐fold. In comparison, CMKLR1 expression in adipocytes of ob/ob mice was reduced 70 % compared to controls. In 3T3‐L1 adipocytes, TNFα treatment produced a dose‐ and time‐dependent induction of chemerin and inhibition of CMKLR1 expression and stimulated the secretion of biologically active chemerin from 3T3‐L1 adipocytes. We conclude that serum chemerin levels are elevated in a mouse model of obesity, which may arise from TNFα‐mediated secretion of chemerin from adipocytes. However, chemerin/CMKLR1 signaling in adipocytes may be blunted in obesity due to reduced expression of CMKLR1. Funding: NSHRF, CIHR, DMRF, DPEF.