Diurnal changes and adaptation by the liver of hamsters to an atherogenic diet

Studies were performed in freely feeding, male (F1B) Syrian hamsters fed a high-fat diet to determine the extent and manner of adaptation of the liver to diurnal changes in eating patterns and an increase in serum lipids. Serum cholesterol and triglycerides strongly paralleled changes in food consumption and were 40-50% greater during the 12-h dark period than the 12-h light period of the diurnal cycle. Hepatic cholesterol changes closely approximated changes in serum cholesterol (r = 0.916) due principally to changes in hepatic cholesteryl esters that were on average about 10-fold greater with the high-fat diet than with a chow diet. With the high-fat diet, hepatic cholesteryl esters were, however, extremely variable and were 40% greater at the mid-dark than at the mid-light period. With high fat there was also a marked increase in the secretion of very low density lipoproteins (VLDL) from the liver that were cholesteryl ester rich and closely paralleled the diurnal changes in hepatic cholesteryl esters (r = 0.911). In contrast, although with a high-fat diet biliary cholesterol secretion was increased, the increase in cholesterol in bile exhibited no diurnal pattern and with the high-fat diet was far less in magnitude than the increase of cholesterol in VLDL. Biliary cholesterol secretion is dependent on bile acid secretion. However, with the high-fat diet, neither the bile acid pool size nor bile acid secretion was increased compared with chow-fed controls. Moreover, with high fat at mid-dark period, bile acid secretion was significantly less than controls at mid-dark period. Thus in these hamsters a high-fat diet produced a marked increase in serum cholesterol that was distinctly diurnal and was compensated for by a diurnal increase in hepatic cholesteryl ester stores and the secretion of cholesteryl esters in VLDL. In contrast, cholesterol secretion in bile did not correspond to the fluctuating changes of cholesterol in the liver and was far less in magnitude than would be necessary to reduce a greatly expanded pool of hepatic cholesterol.