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Dietary Fat-Dependent changes in Hepatic Cholesterogenesis and the Activity of 3-Hydroxy-3-Methylglutaryl-CoA Reductase in Fasted-Refed Rats¹

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

Effects of various dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and sterol and fatty acid synthesis from [1-¹⁴C]acetate and [2-¹⁴C]mevalonate were examined in the liver from fasted-refed rats. Rats fasted for 2 days were refed a fat-free diet or diets containing various fats (tricaprylin, trilaurin, trimyristin, tristearin, camellia oil, or safflower oil) at the 10% level for 1, 3, or 7 days. The activity of HMG-CoA reductase was restored to about one-half of the prefasting levels in all groups after refeeding for 1 day and increased to above the pre-fasting levels after 3 days, with the exception of safflower oil, the rise was especially noticeable when fat-free, tricaprylin, and tristearin diets were fed. After 7 days, the activity of HMG-CoA reductase, except for rats refed tristearin, was decreased to levels that were far below those observed after 1 day-refeeding. This was particularly marked with tricaprylin, trilaurin, and camellia oil. The response of sterogenesis resembled that of the reductase. Dietary fat-dependent modification of fatty acid synthesis from [1-¹⁴C]acetate was first demonstrated after 7 days. Hepatic esterified cholesterol tended to accumulate and the deposition was marked after 3 days of refeeding. However, fat-dependent alterations of this parameter were remarkable on day 7. The concentration of plasma cholesterol also showed dietary fat-dependent changes after refeeding. Dietary fats appear to play an important role not only in the regulation of hepatic HMG-CoA reductase and sterol synthesis, but also in the overall processes of cholesterol dynamics.

KEY WORDS: • HMG-CoA reductase • hepatic sterogenesis • fasting-refeeding • dietary fats

¹ This study was supported in part by the research grant from the Ministry of Education, Science and Culture (Scientific Research (C) No. 356062 to M.S.).

Manuscript received 18 August 1978.