Alteration of the Degree of Biliary Cholesterol Saturation in the Hamster and Rat by Manipulation of the Pools of Preformed and Newly Synthesized Cholesterol

Our studies compared the effects of changing the availability of newly synthesized and preformed cholesterol by various dietary manipulations on biliary cholesterol secretion in the hamster and rat. In hamsters fed a plain pelleted diet, only 2%-5% of biliary cholesterol was derived directly from newly synthesized sterol. Cholestyramine feeding, through a stimulation of hepatic sterol synthesis, increased this fraction fivefold but did not change total biliary cholesterol output. The relative cholesterol content increased significantly due to a reduction in bile acid and phospholipid output. In contrast, biliary cholesterol output was increased several-fold in hamsters fed a fat-free diet. These animals also manifested a pronounced increase in whole-body sterol synthesis, this being due principally to an increase in hepatic sterol synthesis. Although this resulted in the transport of much more newly synthesized cholesterol directly into bile, this did not account for the disproportionately high rate of biliary cholesterol output. Such excess sterol was derived predominantly from a preformed source. Unlike hamsters, rats fed the fat-free diet manifested a marked reduction in hepatic and whole-body sterol synthesis, bile acid pool size, and bile acid and cholesterol output in bile. These studies demonstrate that when hepatic cholesterol synthesis increases in response to a need for more sterol in the body, a greater proportion of biliary cholesterol is derived directly from newly synthesized sterol, but total biliary cholesterol output is unchanged. In contrast, when more cholesterol is synthesized than is needed to maintain cholesterol balance, biliary cholesterol output may increase. Such excess biliary sterol is derived predominantly from a preformed source rather than from the transport of newly synthesized sterol directly across the canalicular membrane.