HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schwarz, M. Articles by Turley, S. D. Search for Related Content PubMed PubMed Citation Articles by Schwarz, M. Articles by Turley, S. D. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 42, 1594-1603, October 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Alternate pathways of bile acid synthesis in the cholesterol 7-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding

Correspondence to: Stephen D. Turley, To whom correspondence should be addressed., stephen.turley{at}utsouthwestern.edu (E-mail)

Bile acids are synthesized via the classic pathway initiated by cholesterol 7-hydroxylase (CYP7A1), and via alternate pathways, one of which is initiated by sterol 27-hydroxylase (CYP27). These studies used mice lacking cholesterol 7-hydroxylase (Cyp7a1^-/-) to establish whether the loss of the classic pathway affected cholesterol homeostasis differently in males and females, and to determine if the rate of bile acid synthesis via alternate pathways was responsive to changes in the enterohepatic flux of cholesterol and bile acids. In both the Cyp7a1^-/- males and females, the basal rate of bile acid synthesis was only half of that in matching Cyp7a1^+/+ animals. Although bile acid pool size contracted markedly in all the Cyp7a1^-/- mice, the female Cyp7a1^-/- mice maintained a larger, more cholic acid-rich pool than their male counterparts. Intestinal cholesterol absorption in the Cyp7a1^-/- males fell from 46% to 3%, and in the matching females from 58% to 17%. Bile acid synthesis in Cyp7a1^+/+ males and females was increased 2-fold by cholesterol feeding, and 4-fold by cholestyramine treatment, but was not changed in matching Cyp7a1^-/- mice by either of these manipulations. In the Cyp7a1^-/- mice fed cholesterol, hepatic cholesterol concentrations increased only marginally in the males, but rose almost 3-fold in the females. CYP7A1 activity and mRNA levels were greater in females than in males, and were increased by cholesterol feeding in both sexes. CYP27 activity and mRNA levels did not vary as a function of CYP7A1 genotype, gender, or dietary cholesterol intake.

We conclude that in the mouse the rate of bile acid synthesis via alternative pathways is unresponsive to changes in the enterohepatic flux of cholesterol and bile acid, and that factors governing gender-related differences in bile acid synthesis, pool size, and pool composition play an important role in determining the impact of CYP7A1 deficiency on cholesterol homeostasis in this species. — Schwarz, M., D. W. Russell, J. M. Dietschy, and S. D. Turley. Alternate pathways of bile acid synthesis in the cholesterol 7-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding. J. Lipid Res. 2001. 42: 1594–1603.

Supplementary key words: bile acid pool size, biliary bile acid, biliary cholesterol, cholesterol absorption, cholesterol synthesis, fecal sterol excretion, liver, small intestine, sterol 27-hydroxylase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. K. Deo and S. M. Bandiera Identification of Human Hepatic Cytochrome P450 Enzymes Involved in the Biotransformation of Cholic and Chenodeoxycholic Acid Drug Metab. Dispos., October 1, 2008; 36(10): 1983 - 1991. [Abstract] [Full Text] [PDF]

				K. R. Wilund, L. A. Feeney, E. J. Tomayko, H. R. Chung, and K. Kim Endurance exercise training reduces gallstone development in mice J Appl Physiol, March 1, 2008; 104(3): 761 - 765. [Abstract] [Full Text] [PDF]

				G. G. Martin, B. P. Atshaves, A. L. McIntosh, J. T. Mackie, A. B. Kier, and F. Schroeder Liver fatty acid binding protein gene ablation potentiates hepatic cholesterol accumulation in cholesterol-fed female mice Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G36 - G48. [Abstract] [Full Text] [PDF]

				C. Yu, F. Wang, C. Jin, X. Huang, and W. L. McKeehan Independent Repression of Bile Acid Synthesis and Activation of c-Jun N-terminal Kinase (JNK) by Activated Hepatocyte Fibroblast Growth Factor Receptor 4 (FGFR4) and Bile Acids J. Biol. Chem., May 6, 2005; 280(18): 17707 - 17714. [Abstract] [Full Text] [PDF]

				J. N. van der Veen, J. K. Kruit, R. Havinga, J. F. W. Baller, G. Chimini, S. Lestavel, B. Staels, P. H. E. Groot, A. K. Groen, and F. Kuipers Reduced cholesterol absorption upon PPAR{delta} activation coincides with decreased intestinal expression of NPC1L1 J. Lipid Res., March 1, 2005; 46(3): 526 - 534. [Abstract] [Full Text] [PDF]

				M. Tiemann, Z. Han, R. Soccio, J. Bollineni, S. Shefer, E. Sehayek, and J. L. Breslow Cholesterol feeding of mice expressing cholesterol 7{alpha}-hydroxylase increases bile acid pool size despite decreased enzyme activity PNAS, February 17, 2004; 101(7): 1846 - 1851. [Abstract] [Full Text] [PDF]

				V. A. B. Drover and L. B. Agellon Regulation of the Human Cholesterol 7{alpha}-Hydroxylase Gene (CYP7A1) by Thyroid Hormone in Transgenic Mice Endocrinology, February 1, 2004; 145(2): 574 - 581. [Abstract] [Full Text] [PDF]

				P. A. Dawson, J. Haywood, A. L. Craddock, M. Wilson, M. Tietjen, K. Kluckman, N. Maeda, and J. S. Parks Targeted Deletion of the Ileal Bile Acid Transporter Eliminates Enterohepatic Cycling of Bile Acids in Mice J. Biol. Chem., September 5, 2003; 278(36): 33920 - 33927. [Abstract] [Full Text] [PDF]

				C. Xie, E. G. Lund, S. D. Turley, D. W. Russell, and J. M. Dietschy Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration J. Lipid Res., September 1, 2003; 44(9): 1780 - 1789. [Abstract] [Full Text] [PDF]

				S. K. Erickson, S. R. Lear, S. Deane, S. Dubrac, S. L. Huling, L. Nguyen, J. S. Bollineni, S. Shefer, H. Hyogo, D. E. Cohen, et al. Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice J. Lipid Res., May 1, 2003; 44(5): 1001 - 1009. [Abstract] [Full Text] [PDF]

				C. Galman, I. Arvidsson, B. Angelin, and M. Rudling Monitoring hepatic cholesterol 7{alpha}-hydroxylase activity by assay of the stable bile acid intermediate 7{alpha}-hydroxy-4-cholesten-3-one in peripheral blood J. Lipid Res., April 1, 2003; 44(4): 859 - 866. [Abstract] [Full Text] [PDF]

				B. Goodwin, M. A. Watson, H. Kim, J. Miao, J. K. Kemper, and S. A. Kliewer Differential Regulation of Rat and Human CYP7A1 by the Nuclear Oxysterol Receptor Liver X Receptor-{alpha} Mol. Endocrinol., March 1, 2003; 17(3): 386 - 394. [Abstract] [Full Text] [PDF]

				L. Yao, P. A. Dawson, and L. A. Woollett Increases in biliary cholesterol-to-bile acid ratio in pregnant hamsters fed low and high levels of cholesterol Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G263 - G268. [Abstract] [Full Text] [PDF]

				J. J. Repa, J. M. Dietschy, and S. D. Turley Inhibition of cholesterol absorption by SCH 58053 in the mouse is not mediated via changes in the expression of mRNA for ABCA1, ABCG5, or ABCG8 in the enterocyte J. Lipid Res., November 1, 2002; 43(11): 1864 - 1874. [Abstract] [Full Text] [PDF]

				J. Y. Chen, B. Levy-Wilson, S. Goodart, and A. D. Cooper Mice Expressing the Human CYP7A1 Gene in the Mouse CYP7A1 Knock-out Background Lack Induction of CYP7A1 Expression by Cholesterol Feeding and Have Increased Hypercholesterolemia When Fed a High Fat Diet J. Biol. Chem., November 1, 2002; 277(45): 42588 - 42595. [Abstract] [Full Text] [PDF]

				M. Rudling, B. Angelin, L. Stahle, E. Reihner, S. Sahlin, H. Olivecrona, I. Bjorkhem, and C. Einarsson Regulation of Hepatic Low-Density Lipoprotein Receptor, 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase, and Cholesterol 7{alpha}-Hydroxylase mRNAs in Human Liver J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4307 - 4313. [Abstract] [Full Text] [PDF]

				I. Bjorkhem, Z. Araya, M. Rudling, B. Angelin, C. Einarsson, and K. Wikvall Differences in the Regulation of the Classical and the Alternative Pathway for Bile Acid Synthesis in Human Liver. NO COORDINATE REGULATION OF CYP7A1 AND CYP27A1 J. Biol. Chem., July 19, 2002; 277(30): 26804 - 26807. [Abstract] [Full Text] [PDF]

				L. B. Agellon, V. A. B. Drover, S. K. Cheema, G. F. Gbaguidi, and A. Walsh Dietary Cholesterol Fails to Stimulate the Human Cholesterol 7alpha -Hydroxylase Gene (CYP7A1) in Transgenic Mice J. Biol. Chem., May 31, 2002; 277(23): 20131 - 20134. [Abstract] [Full Text] [PDF]

				M. Schwarz, D. L. Davis, B. R. Vick, and D. W. Russell Genetic analysis of intestinal cholesterol absorption in inbred mice J. Lipid Res., November 1, 2001; 42(11): 1801 - 1811. [Abstract] [Full Text] [PDF]

				M. Schwarz, D. L. Davis, B. R. Vick, and D. W. Russell Genetic analysis of cholesterol accumulation in inbred mice J. Lipid Res., November 1, 2001; 42(11): 1812 - 1819. [Abstract] [Full Text] [PDF]