The Effects of Simvastatin on Free Fatty Acids Profile in Fructose-fed Insulin Resistant Rats

Backgrounds: Type 2 diabetes mellitus is the most common metabolic disease and free fatty acids, as signaling molecules, can play a crucial role in the development of it. Different free fatty acids, through various cell membrane receptors, induce different effects on metabolic pathways and thereby affect insulin sensitivity. Simvastatin is a cholesterol decreasing drug prescribed for hypercholesterolemic patients. Due to the observing insulin-sensitizing effect of simvastatin in our previous study, we decided to evaluate its effects on free fatty acids profile as a probable mechanism for alteration of insulin sensitivity. Methods: Insulin resistance was developed in male Wistar rats by a high fructose diet for 6 weeks. After this period, animals were treated by intragastric injection of simvastatin for two weeks. Blood samples were collected in EDTA treated tubes and plasma was separated. After isolation of free fatty acids from other lipids fractions, free fatty acids profile were analyzed by gas chromatography system. Results: Simvastatin increased the concentrations of medium chains free fatty acids such as hexanoic acid, octanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid. Simvastatin also increased plasma total free fatty acids concentration. Conclusion: The results of this study demonstrated that simvastatin by increasing the level of medium and long-chain free fatty acids can increase insulin secretion; on the other hand, simvastatin by increasing the level of total and saturated free fatty acids, could induce insulin resistance. More studies are necessary for the evaluation of the precise involved mechanisms in simvastatin effects on insulin function.