Diurnal changes in the rate of cholesterogenesis in hepatocytes from fed and starved rats: Effects of precursors and pancreatic hormones in vitro

The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) varied with a diurnal periodicity in hepatocytes prepared at different times from rats accustomed to a controlled feeding and lighting schedule. The rates of sterol synthesis varied in a similar manner but the maximum rate was not synchronous with maximum HMG-CoA reductase activity. The diurnal increase in HMG-CoA reductase activity and sterol synthesis rate started before food was offered to donor animals. Neither insulin nor glucagon had any effect on the diurnal pattern of hepatic sterol synthesis in vitro. Pyruvate inhibited sterol synthesis in hepatocytes prepared during the feeding period but had no effect at other times of day. When food was withheld from donor animals at the beginning of the normal feeding period both HMG-CoA reductase activity and the rate of sterol synthesis rapidly decreased. During this period neither insulin nor lipogenic substrates, alone or in combination, were able to restore the rates of sterol synthesis to normal values. In hepatocytes prepared from animals starved for a longer period (43 h) the decrease in the activity of HMG-CoA reductase was much less than that in the rate of sterol synthesis. In contrast to hepatocytes from fed or short-term-starved animals, the rate of sterol synthesis in these hepatocytes could be increased by glucose or pyruvate.