Chemerin Is a Novel Adipokine Associated with Obesity and Metabolic Syndrome

• Published in: Endocrinology (Philadelphia) Vol. 148; no. 10; pp. 4687 - 4694
• Main Authors: Bozaoglu, Kiymet, Bolton, Kristy, McMillan, Janine, Zimmet, Paul, Jowett, Jeremy, Collier, Greg, Walder, Ken, Segal, David
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.10.2007; Endocrine Society
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Adipocytes - pathology; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adult; Aged; Amino acid sequence; Animal models; Animals; Biological and medical sciences; Blood circulation; Blood plasma; Blood Pressure; Body fat; Body Mass Index; Body size; Cell differentiation; Cell Differentiation - physiology; Chemokines; Chemokines - blood; Chemokines - genetics; Chemokines - metabolism; Chemotactic Factors - blood; Chemotactic Factors - genetics; Chemotactic Factors - metabolism; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Down-Regulation; Food intake; Food processing; Fractionation; Fundamental and applied biological sciences. Psychology; Gene Expression; Gerbillinae; Glucose; Hormones; Humans; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Medical sciences; Mesentery; Metabolic diseases; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - metabolism; Metabolic Syndrome - physiopathology; Mice; Middle Aged; Miscellaneous; Obesity; Obesity - metabolism; Other metabolic disorders; Phenotype; Proteins; Receptors; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Subcutaneous Tissue - metabolism; Triglycerides; Vertebrates: endocrinology; Viscera; Endocrinopathy; Obesity; X Syndrome; Nutrition disorder; Cardiovascular disease; Metabolic diseases; Adipokine; Nutritional status
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2007-0175

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.