Role of Peroxisome Proliferator-activated Receptor Gamma Agonist on Hepatic Oxidative Stress and Insulin Resistance in High Fat Diet Induced Diabetes

Abstract

Peroxisome proliferator-activated receptor-? agonists have beneficial effects in the oxidative stress pathway by improving the endothelial function. Obesity, a major contributor of insulin resistance has a significant probability of type 2 Diabetes Mellitus, elicits oxidative stress that exacerbates the onset and progression of hepatotoxicity. The prospective of the research is to investigate the role of PPAR-? agonist on insulin resistance and hepatocellular damages due to obesity and diabetes.

Albino Wistar (n=40) was categorized into 5 groups; Group I: Rats fed on a normal rat diet; Group II: High fat diet (HFD) induced obese rats (fed on HFD for 8 weeks); Group III: HFD fed rats treated with Rosiglitazone (3 mg/kg) for 7 days; Group IV: T2DM rats induced by HFD and low dose of Streptozotocin (i.p. 35 mg/kg); Group V: T2DM rats treated with Rosiglitazone (3 mg/kg) for 7 days. Insulin resistance was assessed by Serum insulin level and HOMA-IR. Hepatic oxidative stress was estimated by MDA, SOD, Catalase activity and plasma Paraoxonase -1 level. Obesity and T2DM caused a significant raised insulin resistance. There is marked increased MDA and decreased Catalase, SOD and plasma paraoxonase-1 activity. PPAR-g agonist treatment decreased the insulin resistance in both obesity and T2DM rats and reversed and restored antioxidant status.

The results divulge that PPAR-g agonist not only reversed the effect of HFD and T2DM but also impede deleterious effects on hepatocellular damages due to insulin resistance and oxidative stress.