Dietary cholate is required for antiatherogenic effects of ethanol in mouse models.
BACKGROUND
Human consumption of moderate amounts of ethanol is associated with reduced cardiovascular events. Studies examining the effect of ethanol on atherosclerosis in mouse models have yielded conflicting results that may be due to differences in dietary fat and cholate content. To determine if dietary cholate influences ethanol's effect on atherosclerosis, we fed apolipoprotein E-/- and low-density lipoprotein receptor (LDLR)-/- mice different liquid diets with or without ethanol.


METHODS
Apolipoprotein E-/- mice were fed a low-fat or high saturated fat, cholate-containing diet with or without ethanol for 3 to 10 weeks, and LDLR-/- mice were fed a low-fat, high saturated fat, or high saturated fat diet with cholate with or without ethanol for 7 weeks. At the end of the feeding study, aortic root lesion size was determined and compared with serum cholesterol, triglycerides, and high-density lipoprotein cholesterol. Because dietary cholate increases hepatic nuclear factor (NF)-kappaB and ethanol inhibits NF-kappaB, we also examined the effect of ethanol on aortic NF-kappaB binding activity.


RESULTS
Adding ethanol to a low-fat diet had no effect on lesion size. Similarly, ethanol had no effect on lesion size in LDLR-/- mice consuming a high saturated fat diet. Adding ethanol to a high-fat, cholate-containing diet for either strain resulted in a 25% to 50% reduction in lesion size. Dietary cholate increased and ethanol reduced NF-kappaB binding activity in the aorta.


CONCLUSIONS
These results suggest that ethanol inhibits atherosclerosis in the presence of dietary cholate, which may occur via an anti-inflammatory mechanism.
D000428:Alcohol Drinking / Q000473:pathology*; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology* / Q000517:prevention & control; D020355:Cholates / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000473:pathology* / Q000517:prevention & control; D003331:Coronary Vessels / Q000473:pathology; D004036:Diet, Atherogenic; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D020355:Cholates; D008076:Cholesterol, HDL; D004041:Dietary Fats; D016328:NF-kappa B; D014280:Triglycerides; D000431:Ethanol; D002784:Cholesterol