Increasing dietary cholesterol induces different regulation of classic andalternative bile acid synthesis

We investigated the effect of increasing dietary cholesterol on bile acid p ool sizes and the regulation of the two bile acid synthetic pathways (class ic, via cholesterol 7 alpha-hydroxylase, and alternative, via sterol 27-hyd roxylase) in New Zealand white rabbits fed 3 g cholesterol/per day for up t o 15 days. Feeding cholesterol for one day increased hepatic cholesterol 75 % and cholesterol 7 alpha-hydroxylase activity 1.6 times without significan t change of bile acid pool size or sterol 27-hydroxylase activity. After th ree days of cholesterol feeding, the bile acid pool size increased 83% (P < 0.01), and further feeding produced 10%-20% increments, whereas cholestero l 7 alpha-hydroxylase activity declined progressively to 60% below baseline . In contrast, sterol 27-hydroxylase activity rose 58% after three days of cholesterol feeding and remained elevated with continued intake. Bile drain age depleted the bile acid pool and stimulated downregulated cholesterol 7 alpha-hydroxylase activity but did not affect sterol 27-hydroxylase activit y. Thus, increasing hepatic cholesterol does not directly inhibit cholester ol 7 alpha-hydroxylase and initially favors enzyme induction, whereas incre ased bile acid pool is the most powerful inhibitor of cholesterol 7 alpha-h ydroxylase. Sterol 27-hydroxylase is insensitive to the bile acid flux but is upregulated by increasing hepatic cholesterol.