The Effects of Gemfibrozil and Ovariectomy on the Peroxisome Proliferator Activated Receptors (PPARs) in Mice with Experimentally Induced Obesity

Abstract

Effects of gemfibrozil and ovariectomy on Peroxisome Proliferator Activated Receptors (PPARs) activity were studied in obese mice. Ovariectomised and sham operated mice were fed with high fat diet and low fat diet for 15 weeks. Furthermore, gemfibrozil (100 mg/kg) was orally with high fat and low fat diets to the ovariectomised and sham operated mice. Body weights significantly increased in ovariectomised mice compared to sham operated mice (P<0.001) while gemfibrozil supplementation prevented such increase. Steatosis was as well more pronounced in the livers of ovariectomised mice fed with high fat diet compared to sham operated mice. However, liver steatosis was not seen in gemfibrozil supplemented high fat diet fed mice. On the other hand gemfibrozil supplementation slightly increased the liver weights. High fat diet significantly increased liver AST and ALT enzyme levels and serum total cholesterol, triglyceride and VLDL levels while gemfibrozil lowered these parameters. Immunohistochemically, while tissue PPAR-alpha and PPAR-gamma expressions were affected by ovariectomy, diet and gemfibrozil, PPAR-beta expression unchanged. While high fat diet incremented liver PPAR-alpha and PPAR-gamma expressions their levels were reduced following ovariectomy operation. Only high fat diet and only gemfibrozil application increased PPAR-a expression level. PPAR-alpha expression levels were higher in gemfibrozil and high fat diet combined groups compared to all other groups. In conclusion, gemfibrozil reduced abdominal and hepatic fat deposition in mice with high fat diet and ovariectomy.