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Dietary Regulation of Hepatic 3-Hydroxy-3-Methylglutaryl-CoA Reductase and Cholesterol Synthetic Activities in Fasted-Refed Rats

Laboratory of Nutrition Chemistry, Department of Food Science and Technology, Kyushu University School of Agriculture, Fukuoka 812, Japan

Effects of dietary cholesterol, ß-sitosterol and cholestyramine on hepatic HMG-CoA reductase activity and sterogenesis were examined in male rats refed different types and amounts of fats for 3 days after fasting 2 days. Safflower oil (10%) decreased reductase and sterogenic activities more than saturated fat or low fat. Reductase activity and sterogenesis decreased as dietary cholesterol increased; this was not influenced by the type of dietary fat. Although cholesterol as low as 0.01% depressed these activities, more cholesterol was required to deposit cholesterol in the liver. ß-Sitosterol decreased hepatic cholesterol and increased cholesterol excretion as neutral steroids but failed to enhance reductase and sterogenic activities. In contrast, cholestyramine increased these activities to approximately the same level irrespective of the type and amount of dietary fat. Hepatic cholesterol decreased only in rats refed saturated fat; neutral or acidic steroid excretion was greatest in this group. Hepatic cholesterol and enterohepatically circulating cholesterol may not be critical factors in regulating HMG-CoA reductase in fasted-refed rats. Rather, the quantity of bile acids fluxed to the liver appears to influence the reductase activity in this situation. However, analyses of fecal acidic steroids provided no evidence for a relationship between HMG-CoA reductase activity, bile acid metabolism and dietary fat.

KEY WORDS: • HMG-CoA reductase • hepatic sterogenesis • fasting-refeeding • cholesterol • ß-sitosterol • cholestyramine

¹ To whom reprint requests should be sent.

Manuscript received 14 May 1979.