J. Lipid Res.
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A more recent version of this article appeared on July 1, 2004

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J. Lipid Res., doi:10.1194/jlr.M400061-JLR200
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Submitted on February 17, 2004
Revised on March 31, 2004
Accepted on March 31, 2004

n-6 PUFA down-regulate expression of the tricarboxylate carrier in rat liver by transcriptional and post-transcriptional mechanisms

Luisa Siculella, Fabrizio Damiano, Simona Sabetta, and Gabriele Vincenzo Gnoni

Scienze e Tecnologie Biologiche ed Ambientali, Università di Lecce, Lecce, Lecce 73100

Corresponding Author: gabriele.gnoni{at}unile.it

The tricarboxylate (citrate) carrier (TCC), a protein of the mitochondrial inner membrane, is an obligatory component of the shuttle system by which mitochondrial acetyl-CoA is transported into the cytosol, where lipogenesis occurs. The aim of this study was to investigate the molecular basis for the regulation of TCC gene expression by a high-fat, n-6 PUFA-enriched diet. Rats received for up to four weeks a diet enriched with 15% safflower oil, high in linoleic acid (70.4%). We found a gradual decrease of TCC activity and a parallel decline in the abundance of TCC mRNA, the maximum effect occurring after 4 weeks treatment. At this time, the estimated half life of TCC mRNA was the same in the hepatocytes from rats on both diets while the transcriptional rate of TCC mRNA, tested by nuclear run-on assay, was reduced by about 38% in the rats on the safflower oil-enriched diet. The ribonuclease protection assay showed that the ratio of mature to precursor RNA, measured in the nuclei, decreased with the change to the n-6 PUFA diet. These results suggest that administration of n-6 PUFA to rats leads to changes not only in the transcriptional rate of TCC gene, but also in the processing of the nuclear precursor for TCC RNA.


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