Altered bile acid metabolism related to atherosclerosis in alloxan diabetic rats

Normal and alloxan diabetic rats were kept on a 0.25% cholesterol diet for 12 months and the changes in serum cholesterol levels, and fecal excretion of sterols and bile acids were examined to elucidate the influence of changes in bile acid metabolism on manifestations of hypercholesterolemia and development of atheromatous lesions. Diabetic rats fed the cholesterol diet showed increases in bile acid synthesis and in the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio, and developed significant hypercholesterolemia and atheromatous lesions. In contrast, normal rats showed increased bile acids synthesis but a decreased CA/CDCA ratio after feeding with the cholesterol diet, and developed neither hypercholesterolemia nor atheromatous lesions. Fecal sterol excretion and the cholesterol/sitosterol ratio decreased in diabetic rats. Positive correlations were found between the cumulative serum cholesterol level and the atheromatous lesion area, and between the fecal CA/CDCA ratio and the serum cholesterol level, in the latter of which the correlation was higher in rats on the cholesterol diet than in those on the standard diet. These findings suggest that alteration of bile acid metabolism with increases in cholic acid synthesis and CA/CDCA ratio in diabetic rats enhances cholesterol absorption to produce significant hypercholesterolemia, which in turn leads to development of atheromatous lesions.