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The effects of clofibrate on acetyl-CoA carboxylase activity in hepatocytes

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Summary

Cytochemical localization techniques and electron microscopy were used to evaluate the effects of clofibrate on acetyl-CoA carboxylase activity. It was demonstrated that the drug inhibited the activity of acetyl-CoA carboxylase in rat hepatocytes. Although the results in one of these experiments were somewhat variable, it is suggested that the inhibition of acetyl-CoA carboxylase may be the mechanism by which clofibrate exerts its hypolipidemic effects.

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References

  • Avoy, D. R., Swyryd, E. A., Gould, G.: Effects of alpha-p-chlorophenoxy-isobutyryl ethyl ester (CPIB) with and without androsterone on cholesterol biosynthesis in rat liver. J. Lipid Res. 6, 369–376 (1965).

    Google Scholar 

  • Azarnoff, D. L., Tucker, D. R.: The effects of clofibrate on liver enzymes and substrates. Fed. Proc. 25, 388 (1966).

    Google Scholar 

  • Baranova, L. V.: Effect of atromid on some indices of lipid metabolism in patients having hypercholesterinemia. Kardiol. 5, 65–66 (1965).

    Google Scholar 

  • Best, M., Duncan, C.: Hypolipemia and hepatomegaly from ethyl chlorophenoxyisobutyrate (CPIB) in the rat. J. Lab. clin. Med. 64, 634–642 (1964).

    Google Scholar 

  • —: Reduction of serum triglycerides and cholesterol by ethyl-p-chlorophenoxyisobutyrate (CPIB). Amer. J. Cardiol. 15, 230–233 (1965).

    Google Scholar 

  • Cenedella, R. J., Jarrell, J. J., Saxe, L. H.: Effects of ethyl-p-chlorophenoxyisobutyrate, clofibrate, on the plasma and red blood cell free fatty acids of the rat. J. Atheroscler. Res. 8, 903–911 (1968).

    Google Scholar 

  • Chrusciel, T. L., Herman, Z. S., Brus, R., Plech, A., Habczynska, D., Waxna-Bogunska, C.: Influence of clofibrate and vatensol on the development of experimental atherosclerosis in white rats. In: Paoletti, R., ed. Progress in biochemical pharmacology, vol. 4, p. 578–584. Basel: S. Karger 1968.

    Google Scholar 

  • Felt, V., Starks, L.: Metabolic effects of dehydroepiandrosterone and Atromid in patients with hyperlipaemia. Cor. et vasa (Praha) 8, 40–48 (1966).

    Google Scholar 

  • Hess, R., Staubli, W., Reiss, W.: Nature of the hepatomegalic effect produced by ethylchlorophenoxyisobutyrate in the rat. Nature (Lond.) 208, 856–858 (1965).

    Google Scholar 

  • Kallio, V., Sourander, L. B.: Effect of ethyl chlorophenoxyisobutyrate on serum lipids in aged women. Georntol. clin. (Basel) 8, 349–353 (1966).

    Google Scholar 

  • Knuchel, F.: Effect of atromid-S treatment on the serum lipids and lipoprotein. Med. Welt. N., 47, 2530–2536 (1964).

    Google Scholar 

  • Maragoudakis, M. E.: Inhibition of hepatic acetyl coenzyme A carboxylase by hypolipidemic agents. J. biol. Chem. 244, 5005–5013 (1969).

    Google Scholar 

  • Orgain, E. S., Bogdonoff, M. D., Cain, C.: The effect of chlorphenisate with androsterone (atromid) upon serum lipids. J. New Drugs 6, 125 (1966).

    Google Scholar 

  • Paget, G. E.: Experimental studies on the toxicity of atromid with particular reference to fine structural changes in the livers of rodents. J. Atheroscler. Res. 3, 729–736 (1963).

    Google Scholar 

  • Rifkind, B., Begg, T., Bronte-Stewart, B.: Double-blind trial of atromid-S (clofibrate) in patients with peripheral vascular disease. Progr. biochem. Pharmacol. 2, 358–364 (1967).

    Google Scholar 

  • Ryder, E., Gregolin, C., Chang, H., Lane, M. D.: Liver acetyl-CoA carboxylase: Insight into the mechanism of activation by tricarboxylic acids and acetyl-CoA. Proc. nat. Acad. Sci. (Wash.) 57, 1455–1462 (1967).

    Google Scholar 

  • Svoboda, D. J., Azarnoff, D. L.: Response of hepatic microbodies to a hypolipidemic agent, ethyl chlorophenoxyisobutyrate (CPIB). J. Cell Biol. 30, 442–450 (1966).

    Google Scholar 

  • Wakil, S. J., Gibson, D. M.: Studies on the mechanism of fatty acid biosynthesis. VIII. The participation of protein bound biotin in biosynthesis of fatty acids. Biochim. biophys. Acta (Amst.) 41, 122–129 (1960).

    Google Scholar 

  • Yates, R. D., Higgins, J. A., Barrnett, R. J.: Fine structural localization of acetyl coenzyme-A carboxylase in rat hepatocytes. J. Histochem. Cytochem. 17, 379–385 (1969).

    Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy, The University of Texas Medical Branch, Galveston, Texas, USA

    J. B. Harkins & Robert D. Yates

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  1. J. B. Harkins
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  2. Robert D. Yates
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Additional information

Research supported by USPHS Grants HE 12751, NS 05665 and 00690.

Recipient of Career Research Development Award 1K3 GM 28064. The authors would like to express their appreciation to Richard L. Hogg of the Ayerst Laboratories for supplying the drug.

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Harkins, J.B., Yates, R.D. The effects of clofibrate on acetyl-CoA carboxylase activity in hepatocytes. Z.Zellforsch 119, 321–325 (1971). https://doi.org/10.1007/BF00431290

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  • DOI: https://doi.org/10.1007/BF00431290

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