Effects of clofibrate on lipids and fatty acids of mouse liver
Clofibrate administration significantly altered the amount and fatty acid composition of lipids in mouse liver. The net content of phospholipids (PL) increased and that of triacylglycerols (TG) decreased concomitantly with liver enlargement in mice treated for two weeks with this drug (0.5% w/w in the food). The highest increase among PL was in phosphatidylcholine; other components either showed lower increases or, as in the case of sphingomyelin and the plasmalogens, decreased. In all lipid classes the treatment resulted in altered ratios between major saturates, between saturates and monoenes, and between major polyenes. Among these, 20∶3n–6 and 22∶5n–3 increased several-fold, and the 20∶3n–6/20∶4n–6 and 22∶5n–3/22∶6n–3 ratios increased due to a more active formation of the precursors than of the corresponding products. This change affected all glycerolipid classes. Liver sphingomyelin showed a relative enrichment in monoenoic fatty acids like 22∶1 and 24∶1, caused by a net decrease in the amount of saturates, particularly 22∶0 and 24∶0. The stimulated membrane proliferation imposed by clofibrate must increase phospholipid synthesis and, hence, the need for fatty acids. The results suggest that these demands are met mostly by TG acyl groups, either directly or after oxidation/desaturation processes. This was apparently the case for the polyenoic fatty acids of the n-6 and n-3 series. The longer chain (C22 and C24) components decreased, suggesting that their oxidation was stimulated to provide part of the required (C20 and C22) polyenes.
KeywordsFatty Acid Oxidation Clofibrate Clofibric Acid Zellweger Syndrome Monoenoic Fatty Acid
polyunsaturated fatty acids
Unable to display preview. Download preview PDF.
- 1.Stäubli, W., and Hess, R. (1975) Lipoprotein Formation in the Liver Cell. Ultrastructural and Functional Aspects Relevant to Hypolipidemic ActionHypolipidemic Agents (Kritchevsky, D., ed.), Springer-Verlag, Berlin and New York,Hand. Exp. Pharmacol. 41, 229–289.Google Scholar
- 2.Reddy, J.K., and Lalwani, N.D. (1983) Carcinogenesis by Hepatic Peroxisome Proliferators. Evaluation of the Risk of Hypolipidemic Drugs and Industrial Plasticizers to Humans,CRC Crit. Rev. Toxicol. 12, 1–58.Google Scholar
- 17.Tanaka, K., Smith, P.F., Stromberg, P.C., Eydelloth, R.S., Herold, E.G., Grossman, S.J., Erank, J.D., Hertzog, P.R., Sofer, K.A., and Keenan, K.P. (1992) Studies of Early Hepatocellular Proliferation and Peroxisomal Proliferation in Sprague-Dawley Rats Treated with Tumorigenic Doses of Clofibrate,Toxicol. Appl. Pharmacol. 116, 71–77.PubMedCrossRefGoogle Scholar
- 22.Kawashima, Y., Musoh, K., and Kozuka, H. (1990) Peroxisome Proliferators Enhance Linoleic Acid Metabolism in Rat Liver,J. Biol. Chem. 256, 9170–9175.Google Scholar
- 25.Osmundsen, H., Thomassen, M.S., Hiltunen, J.K., and Berge, R.K. (1987) Physiological Role of Peroxisomal β-Oxidation,Peroxisomes in Biology and Medicine (Fahimi, H.O., and Sies, H., eds.), pp. 152–159, Springer-Verlag, Heidelberg and New York.Google Scholar
- 32.Vamecq, J., Vallee, L. Lechene de la Porte, P., Fontaine, M. de Craemer, D., van den Branden, C., Lafont, H., Grataroli, R., and Nalbone, G. (1993) Effect of Various n-3/n-6 Fatty Acid Ratio Contents of High Fat Diets on Rat Liver and Heart Peroxisomal and Mitochondrial β-Oxidation,Biochim. Biophys. Acta 1170, 151–156.PubMedGoogle Scholar