Abstract
Background: Several studies have shown association of fatty acids with type 2 diabetes (T2D), 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 T2D.
Materials and Methods: Twenty-five adult albino male Wistar rats were divided into the following groups:
Healthy, untreated T2D, and T2D rats receiving metformin for 4 weeks with doses of 100, 150, and 200
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 T2D rats were lower than those in healthy rats
(P < 0.05). We also observed that diabetic rats treated with 100 or 150 mg/kg/d of metformin had higher
levels of arachidonic acid and polyunsaturated fatty acids (PUFA) in comparison with the healthy group
(P < 0.05). Moreover, the T2D+Met (150 mg/kg) group showed increased levels of MUFA compared with
the T2D group. Such a difference was seen in levels of arachidonic acid between the T2D+Met 100 mg/
kg group and untreated T2D group. In the group treated with high doses of metformin (200 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 < .05). In untreated T2D group, there were positive
correlations between glucose levels and linoleic acid and PUFA levels (r = 0.707, P = .049 and r = 0.726,
P = .041 respectively). Arachidonic acid levels were positively correlated with glucose levels in T2D rats
treated with 100 mg/kg/d of metformin (r = 0.969, P = .031).
Conclusions: Our study showed that different doses of metformin could have different effects on serum
levels of saturated and unsaturated fatty acids, as 200 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.