Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits.

The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism during the progression and regression of cholesterol-induced atherosclerosis in rabbits. Three hours after intravenous injection of a 200-microCi tracer dose of [2-14C]acetate, metformin (120 mg/kg per os) strongly diminished the radioactivity in all lipid fractions of the aorta of the normal rabbit. The incorporation of acetate into lipids was greater in the fatty streaks of rabbits fed cholesterol for 2 months than in normal aorta, independent of the plasma radioactivity level. There was increased acetate incorporation into all major lipid groups in the fatty streak, with the greatest relative increase in the cholesteryl ester fraction. No change was observed in the acetate incorporation into lipids in atheromatous deposits after pretreatment of cholesterol-fed rabbits for 8 days with metformin. Concomitant treatment for 2 months with metformin in rabbits fed a cholesterol-enriched diet strongly reduced the radioactivity of total aortic lipids 3 h after intravenous injection of labelled acetate. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free cholesterol, free fatty acids, triglycerides and especially esterified cholesterol and phospholipids). In rabbits fed a cholesterol-enriched diet for a period of two months, followed by a normal diet during 12 months, long-term treatment with metformin significantly reduced total lipid radioactivity in the aorta, 3 h after intravenous injection of the 200-microCi tracer dose of [2-14C]acetate. The incorporation of labelled precursor was markedly reduced in the various lipid fractions. These properties, added to others previously described, can to a large extent explain the protective effect of metformin on experimental atherosclerosis.