1945-P: Pioglitazone Promotes the Function of White and Brown Adipose Tissue in Diet-Induced Obese Mice

Abstract

PPARγ agonist pioglitazone is an insulin sensitizer in the treatment of type 2 diabetes. Here, we investigate the effects of pioglitazone on white and brown fat in diet-induced obese mice. After 16-week diet intervention, C57BL/6 mice were divided randomly into three groups: normal chow diet group (NC group), high-fat diet group (HFD group) and high-fat diet + pioglitazone group (HFDP group). Pioglitazone (30-40mg/kg/day) was administered in drinking water for 6 weeks. After 6-week pioglitazone treatment, there was no significant difference in both body weight and fat mass between the HFDP group and the HFD group. However, fasting blood glucose, glucose tolerance and insulin sensitivity were significantly improved in HFDP group. What’s more, the weight of liver and epididymal adipose tissue (eWAT) were not reduced by pioglitazone treatment. However, the weight of brown adipose tissue (BAT) in the HFDP group was significantly higher than HFD group. Histological staining showed that the hepatic steatosis was ameliorated by pioglitazone. Quantitative real-time PCR revealed that mRNA levels of heat-producing genes (PRDM16, FGF-21, UCP1) and mitochondrial biosynthesis and functional genes (Tfam, cidea, cox7a1, Fabp4) were upregulated in eWAT by pioglitazone. Western blotting results also showed that the protein expression of UCP1 and PGC1α was upregulated by pioglitazone both in eWAT and in BAT when compared with the HFD group. To sum up, our study revealed that pioglitazone could promote the browning of WAT and activate the function of BAT with improved hepatic steatosis in diet-induced obese mice. Disclosure F. Xu: None. W. Wang: None. X. Zheng: None. W. Guo: None. Y. Shen: None.