Resveratrol alleviates obesity-associated podocyte injury in ovariectomized obese rats.

Abstract

Obesity-associated podocyte injury increases in parallel with inflammatory responses. Resveratrol, as an anti-inflammatory and antioxidative agent, has been proven to be effective in obesity. The purpose of the present study was to investigate the function of resveratrol in the early stages of podocyte injury in ovariectomized rats fed a high-fat diet (HFD). The 3-month-old female Wistar rats were randomly divided into four groups: Sham operation with a standard diet; sham operation with a HFD; ovariectomy with a HFD (O+H); and ovariectomy plus HFD treatment with resveratrol (40 mg/kg/day) (O+H+R). Following 12 weeks, the weights of the rats were measured and serum was obtained to measure the levels of 17β-estradiol (E2), serum lipids, serum creatinine, fasting blood glucose (FBG) and insulin. Periodic acid-schiff staining was used to detect renal pathological changes. Meanwhile, the expression of the podocyte-associated proteins nephrin and Wilms' tumor-1 was investigated using immunohistochemical staining, and the levels of tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein-1 in renal tissues were determined using western blotting. Compared with the O+H group, resveratrol significantly reduced the body weight, serum levels of total cholesterol, low-density lipoprotein cholesterol, FBG and insulin resistance, and increased the levels of E2 in obese rats with an ovariectomy combined with an HFD (P<0.05). Compared with the O+H group, although the O+H+R group had no significant changes in renal pathology, the changes in the levels of podocyte-associated proteins and inflammatory markers were significantly reversed (P<0.05). These results suggest that resveratrol may attenuate early podocyte injury by improving lipid metabolism and insulin sensitivity, and subsequently inhibiting inflammatory responses in obese rats induced by an ovariectomy with a HFD.