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Correspondence to:
Stephen D. Turley.
These studies used mice that were deficient in cholesterol 7
This study demonstrates the complex interactions between bile acid and cholesterol metabolism and the dramatic effects of eliminating a single gene product; however, even though a major catabolic pathway was deleted, cholesterol balance across the animal was maintained.—Schwarz, M., D. W. Russell, J. M. Dietschy, and S. D. Turley. Marked reduction in bile acid synthesis in cholesterol 7
Supplementary key words:
cholesterol 7
Copyright © 1998 by Lipid Research, Inc.
Original Article
Marked reduction in bile acid synthesis in cholesterol 7
Margrit Schwarza,
David W. Russella,
John M. Dietschyb, and
Stephen D. Turleyb
-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia
a Departments of Molecular Genetics Internal Medicine, Dallas, TX 75235
b Departments of Molecular Genetics The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235
-hydroxylase to determine the effects of reduced bile acid synthesis on cholesterol homeostasis. In mice lacking this enzyme, bile acid synthesis was reduced from 8.3 to 3.4 µmol/day per 100 g body weight, the intestinal bile acid pool was decreased from 62.5 to 13.2 µmol/100 g bw, and the proportion of hyodeoxycholate, relative to cholate, in this pool was significantly increased. Associated with these changes, intestinal cholesterol absorption decreased from 37% to <1% while triacylglycerol absorption and animal weight gain remained essentially unaffected. The very low rate of cholesterol absorption could be corrected by feeding the mutant mice cholate, but not hyodeoxycholate. The reduction in sterol uptake across the intestine was associated with a 2-fold increase in cholesterol synthesis in the small bowel and liver and an increase in fecal neutral sterol excretion from 15.2 to 35.7 µmol/day per 100 g bw. The size of the cholesterol pools in the plasma, various organs and whole animal remained constant. Thus, under circumstances where the excretion of sterol as bile acids was markedly reduced, total cholesterol turnover actually increased from 164 to 239 mg/day per kg bw. -hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia. J. Lipid Res. 1998. 39: 1833–1843. -hydroxylase, cholesterol absorption, cholesterol synthesis, bile acid pool size, liver, small intestine
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J. J. Repa, S. D. Turley, J.-M. A. Lobaccaro, J. Medina, L. Li, K. Lustig, B. Shan, R. A. Heyman, J. M. Dietschy, and D. J. Mangelsdorf Regulation of Absorption and ABC1-Mediated Efflux of Cholesterol by RXR Heterodimers Science, September 1, 2000; 289(5484): 1524 - 1529. [Abstract] [Full Text]
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C. Xie, S. D. Turley, and J. M. Dietschy Centripetal cholesterol flow from the extrahepatic organs through the liver is normal in mice with mutated Niemann-Pick type C protein (NPC1) J. Lipid Res., August 1, 2000; 41(8): 1278 - 1289. [Abstract] [Full Text]
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 G. J. Schroepfer Jr. Oxysterols: Modulators of Cholesterol Metabolism and Other Processes Physiol Rev, January 1, 2000; 80(1): 361 - 554. [Abstract] [Full Text] [PDF]
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P. Couture, J. D. Otvos, L. A. Cupples, P. W. F. Wilson, E. J. Schaefer, and J. M. Ordovas Association of the A-204C polymorphism in the cholesterol 7{alpha}-hydroxylase gene with variations in plasma low density lipoprotein cholesterol levels in the Framingham Offspring Study J. Lipid Res., October 1, 1999; 40(10): 1883 - 1889. [Abstract] [Full Text]
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C. D. Jolley, J. M. Dietschy, and S. D. Turley Genetic differences in cholesterol absorption in 129/Sv and C57BL/6 mice: effect on cholesterol responsiveness Am J Physiol Gastrointest Liver Physiol, May 1, 1999; 276(5): G1117 - G1124. [Abstract] [Full Text] [PDF]
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E. Sehayek, C. Nath, T. Heinemann, M. McGee, C. E. Seidman, P. Samuel, and J. L. Breslow U-shape relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness and evidence for extreme interindividual variation in dietary cholesterol absorption in humans J. Lipid Res., December 1, 1998; 39(12): 2415 - 2422. [Abstract] [Full Text]
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J. Li-Hawkins, E. G. Lund, S. D. Turley, and D. W. Russell Disruption of the Oxysterol 7alpha -Hydroxylase Gene in Mice J. Biol. Chem., May 26, 2000; 275(22): 16536 - 16542. [Abstract] [Full Text] [PDF]
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J. J. Repa, E. G. Lund, J. D. Horton, E. Leitersdorf, D. W. Russell, J. M. Dietschy, and S. D. Turley Disruption of the Sterol 27-Hydroxylase Gene in Mice Results in Hepatomegaly and Hypertriglyceridemia. REVERSAL BY CHOLIC ACID FEEDING J. Biol. Chem., December 8, 2000; 275(50): 39685 - 39692. [Abstract] [Full Text] [PDF]
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J. H. Miyake, X.-D. T. Doung, W. Strauss, G. L. Moore, L. W. Castellani, L. K. Curtiss, J. M. Taylor, and R. A. Davis Increased Production of Apolipoprotein B-containing Lipoproteins in the Absence of Hyperlipidemia in Transgenic Mice Expressing Cholesterol 7alpha -Hydroxylase J. Biol. Chem., June 22, 2001; 276(26): 23304 - 23311. [Abstract] [Full Text] [PDF]
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E. Sehayek, S. Shefer, L. B. Nguyen, J. G. Ono, M. Merkel, and J. L. Breslow Apolipoprotein E regulates dietary cholesterol absorption and biliary cholesterol excretion: Studies in C57BL/6 apolipoprotein E knockout mice PNAS, March 28, 2000; 97(7): 3433 - 3437. [Abstract] [Full Text] [PDF]
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J. M. Dietschy and S. D. Turley Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal J. Lipid Res., August 1, 2004; 45(8): 1375 - 1397. [Abstract] [Full Text] [PDF]
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