Cholesterogenesis from tritiated water in rats: evidence against the existence of diurnal rhythms (2. Effect of meal-feeding).

In the preceding communication (Fears & Morgan, 1976), we demonstrated that the diurnal variation in cholesterogenesis observed when acetate is used as a substrate is not apparent when 3Hz0 is used to measure the overall rate of the pathway. To investigate this difference further, and more fully to control the individual response to food, we have measured the rates of lipogenesis before and after consumption of a meal of a stock laboratory diet. Male rats of the CFY strain were trained for 3 weeks to consume their daily food intake as a meal between 10:OOh and 12:OOh. In each experiment, rats were maintained on a reversed light-cycle with a period of darkness from 04:Wh to 16:OOh. In addition to 3Hz0, sodium [l-'4C]octanoate was used as a substrate for lipogenesis in vivo. Use of this precursor is believed to give a more accurate measurement of lipogenesis from acetyl-CoA than is possible with acetate (Dietschy & McGarry, 1974). Measurements of lipogenesis were made as described in the preceding paper (Fears & Morgan, 1976). The ileum was used for measurements on the small intestine. The concentration of acetyl-CoA in liver was determined by the method of Williamson & Corkey (1969). The first experiment was performed using sodium [l-14C]acetate with liver slices prepared from animals killed at intervals throughout the day. The purpose of this experiment was to demonstrate the conventional diurnal variation in cholesterogenesis so that we could then select the most appropriate times for more detailed study in vivo. Fig. 1 shows that the synthesis of both fatty acids and cholesterol increased, as anticipated, in response to the ingestion of a meal; 10: OOh and 14: OOh were chosen for