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Journal of Lipid Research, Vol. 45, 1333-1340, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

n-6 PUFAs downregulate expression of the tricarboxylate carrier in rat liver by transcriptional and posttranscriptional mechanisms

L. Siculella, F. Damiano, S. Sabetta and G. V. Gnoni¹

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Laboratorio di Biochimica, Università di Lecce, I-73100 Lecce, Italy

¹ To whom correspondence should be addressed. e-mail: 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 4 weeks a diet enriched with 15% safflower oil (SO), which is 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 of treatment. At this time, the estimated half-life of TCC mRNA was the same in the hepatocytes from rats on both diets, whereas the transcriptional rate of TCC mRNA, tested by nuclear run-on assay, was reduced by 38% in the rats on the SO-enriched diet. The RNase 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 PUFAs to rats leads to changes not only in the transcriptional rate of the TCC gene but also in the processing of the nuclear precursor for TCC RNA.

Abbreviations: ACC, acetyl-CoA carboxylase; G6PD, glucose-6-phosphate dehydrogenase; ME, malic enzyme; L-PK, pyruvate kinase; SCD-1, stearoyl-CoA desaturase; SO, safflower oil; TCC, tricarboxylate carrier

Supplementary key words gene modulation • lipogenesis • mRNA turnover • mitochondria • polyunsaturated fatty acids • ribonuclease protection assay • run-on assay • safflower oil

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