Antiobesity and vasoprotective effects of resveratrol in apoE-deficient mice

Abstract

This study was performed to investigate the hypolipidemic, antiobese, and antiatherogenic effects of resveratrol in apoE-deficient mice fed an atherogenic diet (20% fat and 1% cholesterol). These animals were fed an atherogenic diet containing 0.02% lovastatin (w/w) or 0.02% resveratrol (w/w) for 12 weeks. Resveratrol and lovastatin supplementation significantly reduced either the body weight or epididymal fat weight without altering the food intake and food efficiency ratio. Resveratrol significantly decreased the plasma total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) concentrations, apoB/apoA-I ratio, hepatic cholesterol, and triglyceride (TG) contents, whereas significantly it increased the plasma HDL-C concentration compared with the control and lovastatin groups. Plasma and hepatic TG and plasma apoB levels were significantly lower in both the lovastatin and resveratrol groups than in the control group without altering the plasma apoA-I concentration. Both resveratrol and lovastatin significantly decreased hepatic fatty acid and TG synthesis, whereas they increased fatty acid oxidation (β-oxidation) except for the carnitine palmitoyltransferase activity compared with the control group. However, there was no difference in hepatic 3-hydroxyl-3-methylglutaryl-CoA reductase activity among the groups, although hepatic acyl-CoA: cholesterol acyltransferase activity was significantly lower in the lovastatin groups than in the control group. In epididymal adipose tissue, resveratrol supplementation led to an increase in β-oxidation and decrease in TG synthesis, compared with the control group. Tissue morphology revealed that there were dramatic decreases in hepatic lipid droplets and aortic fatty streaks by resveratrol and lovastatin supplementation. This study demonstrates that resveratrol exerts not only antiobesity and hypolipidemic effects, but also protective effects for the liver and aorta through the modulation of lipid metabolism in both the liver and white adipose tissues.

FIG. 1.

Effects of resveratrol supplementation for 12 weeks on the liver (A) and aorta (B, C) morphologies in apoE-deficient mice fed an atherogenic diet. (A) Hematoxylin and eosin (H&E)-stained transverse section of the liver; (B) H&E-stained transverse section of aortic arch; (C) Oil Red O-stained cryosection of aortic arch; advanced fatty plaques containing lipid-rich components were present in the aortic arch, as well as hepatic lipid droplets in the control group, but not in the lovastatin and resveratrol groups (arrows: hepatic lipid droplets and aortic fatty streak. Magnification 200×). Color images available online at www.liebertpub.com/jmf