ABSTRACT
Recently, TNF-alpha was found to play an important role in development of insulin resistance, one of the hallmarks of metabolic syndrome. The current study aimed to investigate the effect of pioglitazone [PIO] and simvastatin [SIM] on serum level of tumor necrosis factor-alpha [TNF-alpha], as well as on the metabolic perturbations and disturbed homeostasis of glucose and lipids in a fructose-induced insulin resistance [HFD] rat model. To this end sixty male Wistar rats were divided into two dietary regimen-groups that lasted for a period of 8 weeks. Ten rats were fed normal chow and served as normal group [control]. Fifty rats were fed a fructose rich chow containing 60% fructose, 5% fat and 20% protein for a period of 8 weeks. Following confirmation of insulin resistance, rats obtained from the latter group were further subdivided into 4 groups [10 rats; each]. GpI: high fructose diet group [HFD]; Gp II: HFD + PIO [10 mg kg-1]; GpIII: HFD + SIM [20 mg kg-1]; Gp IV: HFD + a combination of PIO/SIM for two weeks. Fructose-fed rats developed insulin resistance [IR] as manifested by the significant increase in body weight, serum levels of glucose, glycosylated hemoglobin [HbA1c], insulin, homeostasis model of assessment insulin resistance index [HOMA-IR index], Triglycerides [TG], Total cholesterol [T-Chol], low density lipoprotein cholesterol [LDL-C] and significant decrease in high density lipoprotein cholesterol [HDL-C]. increase in serum TNF-alpha, as well as increased ratios of epidedymal fat/body weight, visceral fat/body weight and liver weight/ body weight were prominent findings in this study. The results revealed a positive correlation between TNF-alpha and HOMA IR-index. Treatment with PIO or SIM significantly reduced serum glucose, insulin HbA1c, TO, T-Chol, LDL-C and increase of HDL-C. A significant decrease in TNF-alpha, were observed, as well as normalization of increased percentage ratios of epidedymal fat/body weight, visceral fat/body weight and liver weight/body weight. Treatment with PIO or SIM significantly improved disturbed glucose metabolism and HOMA-IR index, co-administration of SIM and PIO synergistically enhanced the overall metabolic parameters