title: Effects of dietary cholesterol on bile formation and hepatic processing of chylomicron remnant cholesterol in the rat.
abstract: We have studied the coupling between hepatic uptake of chylomicron remnant cholesteryl ester and biliary excretion of cholesterol and bile acids in rats, after feeding them a cholesterol-free (control) or a high-cholesterol diet (1% wt/wt) for 2 wk. We equipped rats with permanent catheters in the bile duct, duodenum and heart to allow experiments in unanesthetized, unrestrained animals. Cholesterol feeding induced a 20% increase in plasma cholesterol concentration, a threefold increase in hepatic bile acid synthesis and a 27% increase in bile acid pool size, whereas biliary excretion of cholesterol was decreased by 50%. The enlarged bile acid pool contained relatively less cholic acid and more chenodeoxycholic acid and muricholic acids. [3H]cholesteryl ester-labeled chylomicron remnants (150 micrograms protein per rat) were injected intracardially, and blood and bile were collected for a period of 22 hr. Plasma disappearance of remnants was significantly delayed by cholesterol feeding, probably caused by competition with diet-induced beta-very low density lipoproteins for hepatic uptake. In control rats biliary excretion of chylomicron remnant-derived radioactivity (50% in free cholesterol and 50% in bile acids) showed an initial peak 1 hr after injection (2.4% dose per hour). A second peak (90% in bile acids), amounting to 1.5% of the dose per hour, appeared 11 hr after injection. Total 22-hr excretion of 3H was 22% of the dose. In cholesterol-fed rats chylomicron remnant-derived radioactivity appeared more rapidly in bile, with a peak 1 hr after injection, amounting to 3.5% of the dose per hour. In this case radioactivity was mainly present as bile acid. Total excretion in 22 hr was 27% of the dose. We conclude that chylomicron remnant uptake by the liver is efficiently coupled to bile acid synthesis and biliary excretion, thus providing an efficient pathway for removal of intestine-derived cholesterol. After cholesterol feeding, chylomicron remnant cholesteryl ester is more efficiently converted to bile acids, a mechanism which may contribute to the resistance of rats to diet-induced elevation of plasma cholesterol. In contrast, biliary excretion in the form of free cholesterol, the second main excretory pathway, is significantly decreased by a high-cholesterol diet.
authors.affiliation: Department of Pediatrics, University of Groningen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Smit
authors.forename: F
authors.initials: F
authors.lastname: Kuipers
authors.forename: R J
authors.initials: RJ
authors.lastname: Vonk
authors.forename: A M
authors.initials: AM
authors.lastname: Temmerman
authors.forename: S
authors.initials: S
authors.lastname: Jäckle
authors.forename: E E
authors.initials: EE
authors.lastname: Windler
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D002914:Chylomicrons / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D002914:Chylomicrons; D008055:Lipids; D002784:Cholesterol