The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil

Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be h ypocholesterolemic, but appear to exert their effects by different mechanis ms. In this study, the interaction between dietary fish oil (rich in n-3 po lyunsaturated fatty acids) and estrogen in the regulation of hepatic choles terol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17 alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a mar ked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7 alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (mu mol/h/kg b,wt.) in the bile was unchanged in both groups, Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol este rification to cholesteryl ester hydrolysis only in the fish oil-fed animals . Estrogen increased the concentration of cholesterol (mu mol/ml) in the bi le in rats fed the fish oil, but not the low fat diet. However, the cholest erol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the indi vidual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen- treatment and dietary n-3 polyunsaturated fatty acids causes changes in hep atic cholesterol metabolism and biliary lipid secretion in rats, but does n ot increase the excretion of cholesterol from the body. (C) 1999 Elsevier S cience B.V. All rights reserved.