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Effects of perturbations in hepatic free and esterified cholesterol pools on bile acid synthesis, cholesterol 7α-hydroxylase, HMG-CoA reductase, acyl-CoA:Cholesterol acyltransferase and cytosolic cholesteryl ester hydrolase

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Lipids

Abstract

Effects of expansion of the hepatic free cholesterol pool on bile acid and cholesterol metabolism and homeostasis were examined in rats fed cholesterol in high-fat diets or treated with oleyl-p-(n-decyl)-benzenesulfonate (ODS) or progesterone. Cholesterol feeding for 10–16 days, which increased free (33%) and esterified (6-fold) cholesterol, had no effect on cholate synthesis, total bile acid synthesis, or cholate turnover, whereas these activities were increased 60–80% by ODS and progesterone, which produced only small increases (19%) in free cholesterol. Cholesterol feeding reduced β-hydroxy-β-methylglutaryl (HMG)-CoA reductase (72%) and cholesteryl ester hydrolase (48%) and increased acyl-CoA:cholesterol acyltransferase (184%), whereas ODS and progesterone reversed these compensatory responses in cholesterol-fed rats. Cholesterol 7α-hydroxylase was changed no more than 22% by any treatment. A bolus of ODS elevated biliary cholesterol output 41% and shifted biliary bile acid synthesis and composition toward 12-deoxy bile acids. These effects were not seen in ODS-fed or progesterone-treated rats, in which cholesteryl ester stores were depleted. It is concluded that effects of free cholesterol on bile acid synthesis and biliary cholesterol are probably mediated by specific precursor or regulatory pools which can be independently regulated and which represent a relatively small fraction of hepatic free cholesterol.

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Abbreviations

ACAT:

acyl-CoA:cholesterol acyltransferase

C7AH:

cholesterol 7α-hydroxylase

CEH:

cholesteryl ester hydrolase

HPLC:

high-performance liquid chromatography

HMGCR:

β-hydroxy-β-methylglutaryl-CoA reductase

ODS:

oleyl-p-(n-decyl)-benzenesulfonate

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biophysics, McGuire Veterans Administration Hospital, Medical College of Virginia, Virginia Commonwealth University, 23298-0614, Richmond, Virginia

    W. M. Grogan

  2. Division of Gastroenterology, McGuire Veterans Administration Hospital, Medical College of Virginia, Virginia Commonwealth University, 23298-0614, Richmond, Virginia

    M. L. Bailey, D. M. Heuman & Z. R. Vlahcevic

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  1. W. M. Grogan
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  2. M. L. Bailey
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  3. D. M. Heuman
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  4. Z. R. Vlahcevic
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Grogan, W.M., Bailey, M.L., Heuman, D.M. et al. Effects of perturbations in hepatic free and esterified cholesterol pools on bile acid synthesis, cholesterol 7α-hydroxylase, HMG-CoA reductase, acyl-CoA:Cholesterol acyltransferase and cytosolic cholesteryl ester hydrolase. Lipids 26, 907–914 (1991). https://doi.org/10.1007/BF02535976

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  • DOI: https://doi.org/10.1007/BF02535976

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