Pioglitazone And Fenofibrate Cause Insulin Sensitization And Affect Adiponectin Oligomer Composition In High-Fat-Diet SD Rats

BackgroundAdiponcetin is a recently described circulating hormone released primarily by adipose tissue (white and brown). It circulates in the blood at very high concentrations and exists mainly as a hexamer of relatively low molecular weight (LMW) and a larger multimeric structure of high molecular weight (HMW). Plasma adiponectin complexes have distinct biochemical characteristics and HMW adiponectin is thought to be most biologically active in vivo. Peroxisome proliferator-activated receptors (PPARs), transcription factors belonging to the nuclear receptor superfamily, not only regulating the expression of genes involved in metabolism, but also participating in the altered metabolic homeostasis, are essential for adipocytes and adipocytokines.ObjectiveTo investigate the effects of PPARαagonist, PPARγagonist and dual PPARα/γagonists on insulin resistance and adiponcetin oligomer composition in high-fat-diet (HFD) induced obese rats.MethodsSeventy-five male SD rats were randomly divided into 5 groups: chow diet rats as control group (NC group), HFD rats treated with vehicle (HF group), pioglitazone at 10mg/ (kg·d) (PIO group), fenofibrate at 30mg/ (kg·d) (FF group), and combination of the two drugs as pioglitazone at 10mg/ (kg·d) with fenofibrate at 30mg/ (kg·d) (PIO/FF group). N=15 each group unless otherwise indicated. In experiment termination, body weight (BW), free fatty acids (FFA), triglyeride (TG), total cholesterol (TCH), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. Adiponectin in circulating levels and adipose tissue (subcutaneous and visceral fat) were separated by western blot under non-heat-denatured and non-reduced conditions. Total serum adiponectin concentration was measured by ELISA.ResultsBW, FFA, TG, FPG, FINS in HF group were significantly increased while total serum adiponectin, HMW adiponectin and the ratio of HMW in serum and visceral fat, HMW adiponectin in subcutaneous fat were all significantly reduced in contrast with NC group (P<0.05). It showed that in high-fat-diet (HFD) model, fenofitrate combined pioglitazone treatment resulted in significant reductions in HFD-induced augmentation of metabolic parameters such BW, FFA, TG, FPG and FINS levels (P<0.05). Following fenofibrate, HMW adiponectin in serum, HMW adiponectin and the ratio of HMW in visceral fat were all increased (P<0.05). After pioglitazone and the combined treatment, total serum adiponectin, HMW adiponectin and the ratio of HMW in circulating levels and visceral fat were all increased (P<0.05). However, adiponectin oligomer composition in subcutaneous fat was unaffected by these treatments. HMW adiponectin in serum and visceral adipose tissue negatively correlated with BW, FFA, TG, FPG, FINS levels. Further more, the ratio of HMW in serum and visceral fat negatively correlated with FFA and FPG levels.Conclusion1) pioglitazone and fenofibrate treatment improved insulin sensitivity in HFD rats; 2) drug treatment could ameliorate the suppression of adiponectin secretion caused by obesity; 3) drug's insulin sensitization effects might be associated with the up-regulation of adiponectin synthesis and secretion, especially with the enhanced HMW adiponectin component level and the HMW to total ratio from visceral fat depot.