Chemerin, a Novel Adipokine That Regulates Adipogenesis and Adipocyte Metabolism

TLDR

Obesity is a major health issue linked to diabetes, cardiovascular disease, and hypertension, partly through altered adipokine secretion such as the newly identified chemerin, which signals via the CMKLR1 receptor and participates in immune responses. We demonstrate that chemerin and its receptor CMKLR1 are highly expressed in mouse and human adipocytes, that chemerin secretion activates CMKLR1 signaling and chemotaxis, and that knockdown of either protein impairs adipocyte differentiation and alters metabolic gene expression, establishing chemerin as a regulator of adipogenesis and adipocyte metabolism.

Abstract

Obesity is an alarming primary health problem and is an independent risk factor for type II diabetes, cardiovascular diseases, and hypertension. Although the pathologic mechanisms linking obesity with these co-morbidities are most likely multifactorial, increasing evidence indicates that altered secretion of adipose-derived signaling molecules (adipokines; e.g. adiponectin, leptin, and tumor necrosis factor alpha) and local inflammatory responses are contributing factors. Chemerin (RARRES2 or TIG2) is a recently discovered chemoattractant protein that serves as a ligand for the G protein-coupled receptor CMKLR1 (ChemR23 or DEZ) and has a role in adaptive and innate immunity. Here we show an unexpected, high level expression of chemerin and its cognate receptor CMKLR1 in mouse and human adipocytes. Cultured 3T3-L1 adipocytes secrete chemerin protein, which triggers CMKLR1 signaling in adipocytes and other cell types and stimulates chemotaxis of CMKLR1-expressing cells. Adenoviral small hairpin RNA targeted knockdown of chemerin or CMKLR1 expression impairs differentiation of 3T3-L1 cells into adipocytes, reduces the expression of adipocyte genes involved in glucose and lipid homeostasis, and alters metabolic functions in mature adipocytes. We conclude that chemerin is a novel adipose-derived signaling molecule that regulates adipogenesis and adipocyte metabolism.