title: Increasing dietary cholesterol induces different regulation of classic and alternative bile acid synthesis.
abstract: We investigated the effect of increasing dietary cholesterol on bile acid pool sizes and the regulation of the two bile acid synthetic pathways (classic, via cholesterol 7alpha-hydroxylase, and alternative, via sterol 27-hydroxylase) in New Zealand white rabbits fed 3 g cholesterol/per day for up to 15 days. Feeding cholesterol for one day increased hepatic cholesterol 75% and cholesterol 7alpha-hydroxylase activity 1.6 times without significant change of bile acid pool size or sterol 27-hydroxylase activity. After three days of cholesterol feeding, the bile acid pool size increased 83% (P < 0.01), and further feeding produced 10%-20% increments, whereas cholesterol 7alpha-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 drainage depleted the bile acid pool and stimulated downregulated cholesterol 7alpha-hydroxylase activity but did not affect sterol 27-hydroxylase activity. Thus, increasing hepatic cholesterol does not directly inhibit cholesterol 7alpha-hydroxylase and initially favors enzyme induction, whereas increased bile acid pool is the most powerful inhibitor of cholesterol 7alpha-hydroxylase. Sterol 27-hydroxylase is insensitive to the bile acid flux but is upregulated by increasing hepatic cholesterol.
authors.affiliation: Medical Service, Veterans Affairs Medical Center, East Orange, New Jersey 07018-1095, USA.
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Salen
authors.forename: S
authors.initials: S
authors.lastname: Shefer
authors.forename: G S
authors.initials: GS
authors.lastname: Tint
authors.forename: L B
authors.initials: LB
authors.lastname: Nguyen
authors.forename: T S
authors.initials: TS
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Greenblatt
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000494:pharmacology; D053493:Cholestanetriol 26-Monooxygenase; D002791:Cholesterol, Dietary / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism; D004790:Enzyme Induction / Q000502:physiology; D005246:Feedback / Q000502:physiology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D011817:Rabbits; D013250:Steroid Hydroxylases / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D003840:Deoxycholic Acid; D003577:Cytochrome P-450 Enzyme System; D006903:Hydroxymethylglutaryl CoA Reductases; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase