Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity

Chemerin is a chemoattractant adipokine that regulates adipogenesis and may induce insulin resistance. Chemerin serum concentrations are elevated in obese, insulin-resistant, and inflammatory states in vivo. Here we investigate the role of omental (OM) and subcutaneous (SC) adipose tissue chemerin and CMKLR1 messenger RNA (mRNA) expression in human obesity. In addition, we test the hypothesis that changes in chemerin serum concentrations are primarily associated with reduced body fat mass in the context of 3 weight loss intervention studies. Chemerin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which OM and SC chemerin mRNA expression has been analyzed as well as in 3 interventions including 12 weeks of exercise (n = 60), 6 months of calorie-restricted diet (n = 19) studies, and 12 months after bariatric surgery (n = 32). Chemerin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes mellitus and correlates with circulating chemerin, body mass index (BMI), percentage body fat, C-reactive protein, homeostasis model assessment of insulin resistance, and glucose infusion rate in euglycemic-hyperinsulinemic clamps. CMKLR1 mRNA expression was not significantly different between the 2 fat depots. Obesity surgery-induced weight loss causes a significant reduction on both OM and SC chemerin expression. All interventions led to significantly reduced chemerin serum concentrations. Decreased chemerin serum concentrations significantly correlate with improved glucose infusion rate and reduced C-reactive protein levels independently of changes in BMI. Insulin resistance and inflammation are BMI-independent predictors of elevated chemerin serum concentrations. Reduced chemerin expression and serum concentration may contribute to improved insulin sensitivity and subclinical inflammation beyond significant weight loss.