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Effects of Simple Diets on Cholesterol Synthesis in Rat Liver¹

Department of Physiology, Vanderbilt University Medical School, Nashville, Tennessee 37203

Judging from the incorporation of 2-¹⁴C-acetate into cholesterol by perfused rat livers, the relative rates of hepatic cholesterol synthesis under several conditions were as follows: 1) fed laboratory ration throughout, 100; 2) fasting 1 day, 19; 3) fasting with bile fistula 1 day, 81; 4) fasting 2 days, 11; 5) fed a calorie-free diet (cellulose) 2 days, 9; 6) fed the calorie-free diet with 3% cholestyramine 2 days, 174; 7) fed corn oil at 1 kcal/g (in cellulose) 2 days, 17; 8) fed sucrose and starch at 0.25 and 0.75 kcal/g (in cellulose) 2 days, 43; 9) fed casein, bovine serum albumin, and sodium glutamate at about 0.48, 0.47 and 0.06 kcal/g, respectively, 2 days, 55. It is seen that enhanced removal of secreted bile steroids from the enterohepatic circulation (3 vs. 2, 6 vs. 5) is a potent stimulus to cholesterol synthesis. However, 1 day of bile drainage was no greater stimulus than continued laboratory ration feeding (3 vs. 1), suggesting that factors other than escape of bile steroids from the enterohepatic circulation can influence steroid turnover. The flow of bulk through the intestines did not stimulate synthesis (5 vs. 4) showing that mechanical events associated with feeding are not entirely responsible for the effects of the laboratory diet; i.e., chemical properties of the diet are essential to the feeding effect (1 vs. 2 or 4). Dietary carbohydrate and protein both seem to contribute to the stimulatory effect of a laboratory diet (8 and 9 vs. 5). The role of fat in this respect appears to be very different from the other two nutrients (7 vs. 8 and 9).

² E.B.T. has submitted this work to Tennessee State University in partial fulfillment of the requirement for a Master of Science degree.

³ D.M.R. is an Investigator of the Howard Hughes Medical Institute.

Manuscript received 27 August 1970.