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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M600138-JLR200 on June 30, 2006

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Journal of Lipid Research, Vol. 47, 1994-2003, September 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Conjugated linoleic acid and hepatic lipogenesis in mouse: role of the mitochondrial citrate carrier

Alessandra Ferramosca*, Viviana Savy*, Laura Conte*, Sara Colombo{dagger}, Alexandra W. C. Einerhand§ and Vincenzo Zara1,*

* Department of Sciences and Biological and Environmental Technologies, University of Lecce, 73100 Lecce, Italy
{dagger} Consiglio Nazionale delle Ricerche, Institute of Neuroscience, Cellular and Molecular Pharmacology Section and Department of Medical Pharmacology, University of Milan, 20129 Milan, Italy
§ Lipid Nutrition, Loders Croklaan BV, 1520 AA Wormerveer, The Netherlands

Published, JLR Papers in Press, June 30, 2006.

1 To whom correspondence should be addressed. e-mail: vincenzo.zara{at}unile.it

Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid metabolism. In particular, CLA administration to mice reduces body fat mass with a concomitant lipid accumulation in the liver. We investigated the effects of CLA on the activity of the mitochondrial citrate carrier (CIC), which is implicated in hepatic lipogenesis. The transport activity of the CIC, measured both in intact mitochondria and in the proteoliposomes, progressively increased with the duration of CLA feeding. An increase in the CIC activity of ~1.7-fold was found in 16 week CLA-treated mice with respect to control animals. A kinetic analysis showed a 1.6-fold increase in the Vmax of citrate transport but no change in the Km value. Western blot experiments revealed an increase of ~1.7-fold in the expression of CIC after CLA treatment. A strict correlation between the increase in CIC activity and the stimulation of the cytosolic lipogenic enzymes was also found. These data indicate that the CIC may play a role in the onset of hepatic steatosis in CLA-fed mice by supplying the carbon source for de novo fatty acid synthesis.

Supplementary key words tricarboxylate carrier • lipogenic enzymes • hepatic steatosis

Abbreviations: ACC, acetyl-coenzyme A carboxylase; 1,2,3-BTA, 1,2,3-benzenetricarboxylate; CIC, mitochondrial tricarboxylate or citrate carrier; CLA, conjugated linoleic acid; CPT, carnitine palmitoyltransferase


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