title: Chemerin, a novel adipokine that regulates 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.
authors.affiliation: Department of Pharmacology and College of Pharmacy, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
authors.forename: Kerry B
authors.initials: KB
authors.lastname: Goralski
authors.forename: Tanya C
authors.initials: TC
authors.lastname: McCarthy
authors.forename: Elyisha A
authors.initials: EA
authors.lastname: Hanniman
authors.forename: Brian A
authors.initials: BA
authors.lastname: Zabel
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Parlee
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Muruganandan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction
chemical_list: C486456:CMKLR1 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse