Effects of Different Doses of Metformin on Serum Fatty Acid Composition in Type ۲ Diabetic Rats

Background: Several studies have shown association of fatty acids with type ۲ diabetes (T۲D), as well as metformin effects on blood glucose concentrations through affecting lipid metabolism. Objectives: Since the exact therapeutic mechanism of metformin is not clear, in this study we investigated effects of different doses of metformin on serum fatty acids in rats with T۲D. Materials and Methods: Twenty-five adult albino male Wistar rats were divided into the following groups: Healthy, untreated T۲D, and T۲D rats receiving metformin for ۴ weeks with doses of ۱۰۰, ۱۵۰, and ۲۰۰ mg/kg/d. Serum insulin and triglyceride (TG) were measured using commercial kits. Serum total lipids were extracted by the Bligh-Dyer method and then compositions of fatty acids were evaluated using gas chromatograph. Results: Monounsaturated fatty acid (MUFA) levels in T۲D rats were lower than those in healthy rats (P < ۰.۰۵). We also observed that diabetic rats treated with ۱۰۰ or ۱۵۰ mg/kg/d of metformin had higher levels of arachidonic acid and polyunsaturated fatty acids (PUFA) in comparison with the healthy group (P < ۰.۰۵). Moreover, the T۲D+Met (۱۵۰ mg/kg) group showed increased levels of MUFA compared with the T۲D group. Such a difference was seen in levels of arachidonic acid between the T۲D+Met ۱۰۰ mg/ kg group and untreated T۲D group. In the group treated with high doses of metformin (۲۰۰ mg/kg/d), levels of palmitic acid, palmitoleic acid, and saturated fatty acid (SFA) were higher and levels of oleic acid, linoleic acid, arachidonic acid, MUFA, PUFA, and also SFA/UFA ratio were lower compared with other metformin treated and untreated groups (P < .۰۵). In untreated T۲D group, there were positive correlations between glucose levels and linoleic acid and PUFA levels (r = ۰.۷۰۷, P = .۰۴۹ and r = ۰.۷۲۶, P = .۰۴۱ respectively). Arachidonic acid levels were positively correlated with glucose levels in T۲D rats treated with ۱۰۰ mg/kg/d of metformin (r = ۰.۹۶۹, P = .۰۳۱). Conclusions: Our study showed that different doses of metformin could have different effects on serum levels of saturated and unsaturated fatty acids, as ۲۰۰ mg/kg/d of metformin could increase and decrease saturated and unsaturated fatty acids respectively, while lower doses increased unsaturated fatty acids, particularly arachidonic acid.