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Effect of metformin on lipid metabolism in the rabbit aortic wall
Abstract:
The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism. Pretreatment of rabbits for 8 days with 120 mg/kg per os metformin reduced by 50--70% the incorporation of a 20 muCi tracer doseof [4(-14)C]cholesterol (given orally 24 h before) into various segments of aorta, plasma, liver, intestine and lung, as compared with control animals. However, as intestinal absorption of cholesterol was also diminished in the same proportion, it was then decided to inject the labelled cholesterol directly into the blood. Under these conditions, metformin induced the same reduction in [4(-14)C]cholesterol specific activity in the aorta, but not in other tissues. Three hours after intravenous injection of a 200 muCi tracer dose of [2(-14)C]-acetate, metformin strongly diminished the radioactivity of total lipids of the aorta, both in fed-rabbits and in rabbits on a 24 h fast, independently of the plasma radioactivity level. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free and esterified cholesterol, free fatty acids, phospholipids and especially triglycerides) and the effect persisted unaltered over periods of increasing length after the injection of precursor (1/4, 1/2, 1, 3, 5, 8, 12 h). Metformin also significantly inhibited lipid biosynthesis in the liver and intestine. These properties, added to others previously described, can to a large extent explain the preventive effect of metformin on experimental atherosclerosis.
Insights
Metformin significantly reduces aortic lipid metabolism by inhibiting cholesterol and acetate incorporation into arterial lipids. This finding supports metformin's potential role in preventing atherosclerosis.
Area of Science:
- Biochemistry
- Pharmacology
- Cardiovascular Research
Background:
- Atherosclerosis is a major cardiovascular disease characterized by lipid accumulation in arteries.
- Metformin, a common diabetes drug, has shown potential in cardiovascular protection.
- The precise mechanisms by which metformin affects aortic lipid metabolism are not fully understood.
Purpose of the Study:
- To investigate the effect of metformin on aortic lipid metabolism in rabbits.
- To determine if metformin alters cholesterol and acetate incorporation into aortic lipids.
- To explore the impact of metformin on lipid biosynthesis in other organs.
Main Methods:
- Rabbits were pretreated with metformin and administered radiolabeled cholesterol (orally and intravenously) and acetate.
- Lipid incorporation and radioactivity were measured in aorta, plasma, liver, intestine, and lung.
- Specific lipid fractions (cholesterol, fatty acids, phospholipids, triglycerides) were analyzed.
Main Results:
- Metformin reduced cholesterol incorporation into the aorta by 50-70%, regardless of administration route.
- Metformin significantly decreased acetate incorporation into all aortic lipid fractions.
- Inhibition of lipid biosynthesis was also observed in the liver and intestine.
- The effect on acetate incorporation persisted for up to 12 hours.
Conclusions:
- Metformin demonstrably alters aortic lipid metabolism by inhibiting both cholesterol and acetate incorporation.
- These findings suggest that metformin's impact on lipid biosynthesis contributes to its preventive effects on experimental atherosclerosis.
- Metformin's ability to inhibit lipid synthesis in the aorta, liver, and intestine highlights its multifaceted role in cardiovascular health.