TY - JOUR
T1 - Induction of bile acid synthesis by cholesterol and cholestyramine feeding is unimpaired in mice deficient in apolipoprotein AI
AU - Jolley, Christopher D.
AU - Dietschy, John M.
AU - Turley, Stephen D.
N1 - Funding Information:
Abbreviations: HDL-C, high density lipoprotein cholesterol; apo AI, apolipoprotein AI; DPS, digitonin-precipitable sterols; HPLC, high-performance liquid chromatography; SEM, standard error of mean; mRNA, messenger RNA; LXRα, liver X receptor α; NPC-1, Niemann-Pick type C protein. From the Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX. Received June 8, 2000; accepted September 5, 2000. These studies were supported by U.S. Public Health Service Grant R37 HL 09610 and a grant from the Moss Heart Fund. Dr. Jolley was supported by NIH Training Grant T32 DK 07745. Address reprint requests to: Stephen D. Turley, Ph.D., Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8887. E-mail: stephen.turley@utsouthwestern.edu; fax: (214) 648-9761. Copyright © 2000 by the American Association for the Study of Liver Diseases. 0270-9139/00/3206-0017$3.00/0 doi:10.1053/jhep.2000.19811
PY - 2000
Y1 - 2000
N2 - High density lipoprotein (HDL) cholesterol is believed to be preferentially utilized for bile acid synthesis and biliary secretion. In mice, the deletion of apolipoprotein AI (apo AI), the major apolipoprotein in HDL, results in very low plasma HDL-cholesterol levels. This article describes bile acid metabolism in apo AI-deficient (Apo AI(-/-)) mice and their C57BL/6 (Apo AI(+/+)) controls fed either a basal rodent diet alone or containing cholesterol or cholestyramine. Basal plasma HDL-cholesterol levels in the (-/-) mice (<10 mg/dL) were less than 20% of those in their (+/+) controls, but there were no phenotypic differences in either the relative cholesterol content of gallbladder bile, bile acid pool size and composition, fecal bile acid excretion or the activity of, or mRNA level for, cholesterol 7α-hydroxylase. However, compared with their (+/+) controls, the (-/-) mice absorbed more cholesterol (33 vs. 24%) and manifested lower rates of hepatic sterol synthesis (534 vs. 1,019 nmol/h per g). Cholesterol feeding increased hepatic cholesterol levels in the (+/+) animals from 2.7 to 4.4 mg/g and in the (-/-) mice from 2.6 to 8.1 mg/g. Bile acid synthesis increased 70% in both genotypes. Cholestyramine feeding stimulated bile acid synthesis 3.7 fold in both (-/-) and (+/+) mice. We conclude that the virtual loss of HDL-cholesterol from the circulation in apo AI deficiency has no impact on the ability of the hepatocyte to adapt its rate of bile acid synthesis in concert with the amount of cholesterol and bile acid returning to the liver from the small intestine.
AB - High density lipoprotein (HDL) cholesterol is believed to be preferentially utilized for bile acid synthesis and biliary secretion. In mice, the deletion of apolipoprotein AI (apo AI), the major apolipoprotein in HDL, results in very low plasma HDL-cholesterol levels. This article describes bile acid metabolism in apo AI-deficient (Apo AI(-/-)) mice and their C57BL/6 (Apo AI(+/+)) controls fed either a basal rodent diet alone or containing cholesterol or cholestyramine. Basal plasma HDL-cholesterol levels in the (-/-) mice (<10 mg/dL) were less than 20% of those in their (+/+) controls, but there were no phenotypic differences in either the relative cholesterol content of gallbladder bile, bile acid pool size and composition, fecal bile acid excretion or the activity of, or mRNA level for, cholesterol 7α-hydroxylase. However, compared with their (+/+) controls, the (-/-) mice absorbed more cholesterol (33 vs. 24%) and manifested lower rates of hepatic sterol synthesis (534 vs. 1,019 nmol/h per g). Cholesterol feeding increased hepatic cholesterol levels in the (+/+) animals from 2.7 to 4.4 mg/g and in the (-/-) mice from 2.6 to 8.1 mg/g. Bile acid synthesis increased 70% in both genotypes. Cholestyramine feeding stimulated bile acid synthesis 3.7 fold in both (-/-) and (+/+) mice. We conclude that the virtual loss of HDL-cholesterol from the circulation in apo AI deficiency has no impact on the ability of the hepatocyte to adapt its rate of bile acid synthesis in concert with the amount of cholesterol and bile acid returning to the liver from the small intestine.
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U2 - 10.1053/jhep.2000.19811
DO - 10.1053/jhep.2000.19811
M3 - Article
C2 - 11093738
AN - SCOPUS:0033652099
SN - 0270-9139
VL - 32
SP - 1309
EP - 1316
JO - Hepatology
JF - Hepatology
IS - 6
ER -