Fructose induced metabolic syndrome in rats, a role for Glitazones, fibrates and statins

ABSTRACT

The metabolic syndrome is a constellation of symptoms and signs that include central obesity, insulin resistance, dysglycemia. dyslipidemia and hypertension. .The present work aimed to study the effect of a Peroxisome Proliferator Activated Receptor-alpha [PPAR-alpha] agonist [fenofibrate], two PPAR-gamma agonists [rosiglitazone and pioglitazone] and a statin [simvastatin] on glycemic control and lipid profile in fructose-induced metabolic syndrome in rats. The study also aimed to assess the benefits gained from the combination of these agents. The present study was carried out on one hundred and ten white male albino rats. Ten rats received normal laboratory chow. The remaining rats were fed a high fructose diet for induction of metabolic syndrome X. The current study showed that treatment of fructose induced metabolic syndrome [FMS] rats with fenofibrate, rosiglitazone or pioglitazone was associated with significant improvement in glycemic control Fenofibrate treatment was associated with significant decrease in body weight in comparison to rosiglitazone or pioglitazone-treated rats that showed a significant body weight gain. Fenofibrate and simvastatin treatment of FMS rats caused a significant decrease in serum triglycerides [TGs,], cholesterol as well as significant increase in serum high density lipoproteins [HDL]. Only simvastatin resulted in a significant decrease in serum low density lipoproteins [LDL]. The combination of fenofibrate with rosiglitazone or pioglitazone was associated with less body weight gain and a more marked improvement in glycemic control The addition of simvastatin to fenofibrate and rosiglitazone or pioglitazone was associated with a significant improvement in lipid profile when compared to the combination offenofibrate with rosiglitazone or pioglitazone. No further significant improvement in glycemic was control achieved by the addition of simvastatin to nfenofibrate and rosiglitazone or pioglitazone. Given the close relationship between PPAR activity and the metabolic syndrome, PPAR agonists are promising therapeutic agents for diseases including type 2 diabetes mellitus [DM2]. obesity, hypertension, hyperlipidemia and atherosclerosis. Combination drug therapy, which utilizes complementary mechanisms, can be advantageous in patients with significant combined or mixed dyslipidemias. The combination of glitazones and statins was associated with the utmost glycemic control and improvement in lipid profile