Chemerin is a novel adipokine associated with obesity and metabolic syndrome.
Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.
Bozaoglu
Kiymet
K
Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
Bolton
Kristy
K
McMillan
Janine
J
Zimmet
Paul
P
Jowett
Jeremy
J
Collier
Greg
G
Walder
Ken
K
Segal
David
D
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D001794:Blood Pressure; D015992:Body Mass Index; D002454:Cell Differentiation / Q000502:physiology; D018925:Chemokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002630:Chemotactic Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015870:Gene Expression; D005849:Gerbillinae; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008643:Mesentery; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000378:metabolism; D014781:Viscera
C102741:CMKLR1 protein, human; 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