Aerobic exercise-induced decrease of chemerin improved glucose and lipid metabolism and fatty liver of diabetes mice through key metabolism enzymes and proteins.

Our previous studies have implicated an important role of adipokine chemerin in exercise-induced improvements of glycolipid metabolism and fatty liver in diabetes rat, but the underlying mechanisms remain unknown. This study first used an exogenous chemerin supplement to clarify the roles of decreased chemerin in exercised diabetes mice and possible mechanisms of glucose and lipid metabolism key enzymes and proteins [such as adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 4 (GLUT4)]. In addition, two kinds of adipose-specific chemerin knockout mice were generated to demonstrate the regulation of chemerin on glucose and lipid metabolism enzymes and proteins. We found that in diabetes mice, exercise-induced improvements of glucose and lipid metabolism and fatty liver, and exercise-induced increases of ATGL, LPL, and GLUT4 in liver, gastrocnemius and fat were reversed by exogenous chemerin. Furthermore, in chemerin knockdown mice, chemerin(-/-)∙adiponectin mice had lower body fat mass, improved blood glucose and lipid, and no fatty liver; while chemerin(-/-)∙fabp4 mice had hyperlipemia and unchanged body fat mass. Peroxisome proliferator-activated receptor γ (PPARγ), ATGL, LPL, GLUT4 and PEPCK in the liver and gastrocnemius had improve changes in chemerin(-/-)·adiponectin mice while deteriorated alterations in chemerin(-/-)·fabp4 mice, although PPARγ, ATGL, LPL, and GLUT4 increased in the fat of two kinds of chemerin(-/-) mice. CONCLUSIONS: Decreased chemerin exerts an important role in exercise-induced improvements of glucose and lipid metabolism and fatty liver in diabetes mice, which was likely to be through PPARγ mediating elevations of ATGL, LPL and GLUT4 in peripheral metabolic organs.