The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 α-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT)] were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 α-hydroxylase activity was decreased by 55–60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Miettinen T (1986) Cholesterol balance and lipoprotein metabolism in man. Atheroscler Rev 15: 113–155
Einarsson K, Angelin B (1986) Hyperlipoproteinemia, hypolipidemic treatment, and gallstones disease. Atheroscler Rev 15: 67–97
Eisenberg S, Gavish D, Oschry Y, Fainaru M, Deckelbaum RJ (1984) Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia.: reversal toward normal with bezafibrate treatment. J Clin Invest 74: 470–482
Bergmann K von, Leiss O (1984) Effect of short-term treatment with bezafibrate and fenofibrate on biliary lipid metabolism in patients with hyperlipoproteinaemia. Eur J Clin Invest 14: 150–154
Leiss O, Meyer-Krahmer K, Bergmann K von (1986) Biliary lipid secretion in patients with heterozygous familial hypercholesterolemia and combined hyperlipidemia. Influence of bezafibrate and fenofibrate. J Lipid Res 27: 713–723
Grundy SM, Ahrens EH Jr, Salen G, Schreibman PH, Nestel PJ (1972) Mechanisms of action of clofibrate on cholesterol metabolism in patients with hyperlipidemia. J Lipid Res 13: 531–551
Einarsson K, Hellström K, Kallner M (1973) The effect of clofibrate on the elimination of cholesterol as bile acids in patients with hyperlipoproteinaemia types II and IV. Eur J Clin Invest 3: 345–351
Eriksson M, Angelin B (1987) Bezafibrate therapy and biliary lipids: effects of short-term and long-term treatment in patients with various forms of hyperlipoproteinaemia. Eur J Clin Invest 17: 396–401
Angelin B, Einarsson K, Leijd B (1981) Clofibrate treatment and bile cholesterol saturation: short-term and long-term effects and influence of combination with chenodeoxycholic acid. Eur J Clin Invest 11: 185–189
Cohen BI, Raicht RF, Shefer S, Mosbach EH (1974) Effects of clofibrate on sterol metabolism in the rat. Biochim Biophys Acta 369: 79–85
Turley SD, Dietschy JM (1980) Effects of clofibrate, cholestyramine, zanchol, probucol, and AOMA feeding on hepatic and intestinal cholesterol metabolism and on biliary lipid secretion in the rat. J Cardiovasc Pharmacol 2: 281–297
Angelin B, Björkhem I, Einarsson K (1976) Effects of clofibrate on some microsomal hydroxylations involved in the formation and metabolism of bile acids in rat liver. Biochem J 156: 445–448
Ståhlberg D, Angelin B, Einarsson K (1989) Effects of treatment with clofibrate, bezafibrate, and ciprofibrate on the metabolism of cholesterol in rat liver microsomes. J Lipid Res 30: 953–958
Angelin B, Einarsson K, Liljeqvist L, Nilsell K, Heller RA (1984) 3-Hydroxy-3-methylglutaryl coenzyme A reductase in human liver microsomes: active and inactive forms and cross-reactivity with antibody against rat liver enzyme. J Lipid Res 25: 1159–1166
Einarsson K, Angelin B, Ewerth S, Nilsell K, Björkhem I (1986) Bile acid synthesis in man: assay of hepatic microsomal cholesterol 7 alpha-hydroxylase activity by isotope dilution-mass spectrometry. J Lipid Res 27: 82–88
Einarsson K, Benthin L, Ewerth S, Hellers G, Ståhlberg D, Angelin B (1989) Studies on acyl-coenzyme A: cholesterol acyltransferase activity in human liver microsomes. J Lipid Res 30: 739–746
Björkhem I, Blomstrand R, Svensson L (1974) Serum cholesterol determination by mass fragmentography. Clin Chim Acta 54: 185–193
Angelin B, Einarsson K (1985) Regulation of HMG-CoA reductase in human liver. In: Preiss B (ed) Regulation of HMG-CoA reductase. Academic Press, New York, pp 281–320
Ståhlberg D, Reihnér E, Rudling M, Berglund L, Einarsson K, Angelin B (1990) Effects of bezafibrate on hepatic cholesterol metabolism in man. (submitted for publication)
Rudling MJ, Peterson CO (1985) A simple binding assay for the determination of low-density lipoprotein receptors in cell homogenates. Biochim Biophys Acta 833: 359–365
Björkhem I, Miettinen T, Reihnér E, Ewerth S, Angelin B, Einarsson K (1987) Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver. J Lipid Res 28: 1137–1143
Stewart JM, Packard CJ, Lorimer AR, Boag DE, Sheperd J (1982) Effects of bezafibrate on receptor-mediated and receptor-independent low density lipoprotein catabolism in type II hyperlipoproteinaemic subjects. Atherosclerosis 44: 355–365
About this article
Cite this article
Ståhlberg, D., Reihnér, E., Ewerth, S. et al. Effects of bezafibrate on hepatic cholesterol metabolism. Eur J Clin Pharmacol 40, S33–S36 (1991). https://doi.org/10.1007/BF03216286
- HMG-CoA reductase
- cholesterol 7 α-hydroxylase