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Submitted on February 7, 2007
Accepted on July 9, 2007
Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Waurn Ponds, Victoria, Australia, International Diabetes Institute, Caulfield, Victoria, Australia, ChemGenex Pharmaceuticals, Geelong, Victoria, Australia
* To whom correspondence should be addressed. E-mail: dsegal{at}deakin.edu.au.
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 (SST) 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 SST, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, CMKLR1, were significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared to lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes while CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation while 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 type 2 diabetes 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 is associated with several key aspects of metabolic syndrome.
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