Metformin improves lipid metabolism and attenuates lipid peroxidation in high fructose-fed rats

Aim: Insulin resistance, hyperinsulinaemia and disturbances in glucose metabolism can be produced in normal rats by feeding them a fructose-enriched diet. Metformin, an antidiabetic drug, enhances insulin sensitivity in type 2 diabetic patients. Previous studies have shown that metformin improves insulin sensitivity in fructose-fed rats. The aim of this study was to determine the effect of metformin treatment on overall lipid metabolism and lipid peroxidation in rats that were fed a fructose-enriched diet, which leads to insulin resistance. The relationship between hyperinsulinaemia and hyperglycaemia with lipid peroxide levels was also investigated. Materials and Methods: The animals were divided into two batches. One batch received a standard diet and the other was fed a fructose-enriched diet (72 g/100 g feed). After 2 weeks, each batch of rats was subdivided into two groups. One group received metformin (50 mg/kg per day in water) and the other received the standard diet and served as control. Results: High fructose feeding resulted in hyperinsulinaemia, hvperglycaemia and alterations in lipids and lipid metabolism. and plasma and tissue lipid peroxides were significantly elevated. Administration of metformin (50 mg/kg/day) was associated with significant normalization of plasma insulin level and lipid alterations. These rats also showed significantly higher lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) activities in plasma than untreated, fructose-fed rats. Lipid peroxides content was also decreased in plasma and tissues, Significant positive correlations were observed between the levels of plasma insulin and plasma glucose with plasma lipid peroxides. Conclusions: We conclude that enhanced lipid peroxidation occurs in addition to disturbances in lipid metabolism in fructose-fed rats. Plasma insulin level probably contributes to this increased peroxidation. Improved insulin action in metformin-treated rats could be responsible for the amelioration of these abnormalities induced by fructose feeding.