Dietary fish oil-induced changes in intrahepatic cholesterol transport and bile acid synthesis in rats.
Hepatic cholesterol metabolism was studied in rats fed purified diets supplemented (9% wt/wt) with either fish oil (FO) (n-3 fatty acids) or corn oil (CO) (n-6 fatty acids) for 4 wk. Rats were equipped with permanent catheters in heart, bile duct, and duodenum to allow studies under normal feeding conditions. [3H]-cholesteryl oleate-labeled small unilamellar liposomes, which are rapidly endocytosed by hepatocytes, were intravenously injected to label intrahepatic cholesterol pools, and plasma and bile were collected. FO as compared to CO induced a lowering of plasma cholesterol levels by 38% and of triglyceride levels by 69%. This reduction in plasma lipids in FO rats was accompanied by: (a) an increased bile acid pool size (28%); (b) a fourfold increase in the ratio cholic acid/chenodeoxycholic acid in bile; (c) increased biliary excretion of cholesterol (51%); (d) accelerated excretion of endocytosed free cholesterol into bile; (e) accelerated incorporation of endocytosed cholesterol in bile acids; (f) a significant increase in the bile acid-independent fraction of bile flow; and (g) a threefold increase in hepatic alkaline phosphatase activity. The results show that FO induces changes in transport and metabolic pathways of cholesterol in the rat liver, which result in a more rapid disposition of plasma-derived cholesterol into the bile.
Smit
M J
MJ
Department of Pediatrics, University of Groningen, The Netherlands.
Temmerman
A M
AM
Wolters
H
H
Kuipers
F
F
Beynen
A C
AC
Vonk
R J
RJ
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis / Q000096:biosynthesis*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D003314:Corn Oil / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D004041:Dietary Fats; D005395:Fish Oils; D008055:Lipids; D008074:Lipoproteins; D003314:Corn Oil; D002784:Cholesterol; D000469:Alkaline Phosphatase