Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism.
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.
Goralski
Kerry B
KB
Department of Pharmacology and College of Pharmacy, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
McCarthy
Tanya C
TC
Hanniman
Elyisha A
EA
Zabel
Brian A
BA
Butcher
Eugene C
EC
Parlee
Sebastian D
SD
Muruganandan
Shanmugam
S
Sinal
Christopher J
CJ
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
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