Liver carnitine palmitoyltransferase I (L-CPT I) catalyses the transfer of long-chain fatty acid (LCFA) for translocation across the mitochondrial membrane. Expression of the L-CPT I gene is induced by LCFAs as well as by lipid-lowering compounds such as clofibrate. Previous studies have suggested that the peroxisome-proliferator-activated receptor α (PPARα) is a common mediator of the transcriptional effects of LCFA and clofibrate. We found that free LCFAs rather than acyl-CoA esters are the signal metabolites responsible for the stimulation of L-CPT I gene expression. Using primary culture of hepatocytes we found that LCFAs failed to stimulate L-CPT I gene expression both in wild-type and PPARα-null mice. These results suggest that the PPARα-knockout mouse does not represent a suitable model for the regulation of L-CPT I gene expression by LCFAs in the liver. Finally, we determined that clofibrate stimulates L-CPT I through a classical direct repeat 1 (DR1) motif in the promoter of the L-CPT I gene while LCFAs induce L-CPT I via elements in the first intron of the gene. Our results demonstrate that LCFAs can regulate gene expression through PPARα-independent pathways and suggest that the regulation of gene expression by dietary lipids is more complex than previously proposed.
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February 2001
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Research Article|
February 08 2001
Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway
Jean-Francç;ois LOUET;
Jean-Francç;ois LOUET
1
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Florence CHATELAIN;
Florence CHATELAIN
1
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Jean-Francç;ois DECAUX;
Jean-Francç;ois DECAUX
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Edwards A. PARK;
Edwards A. PARK
2
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Claude KOHL;
Claude KOHL
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Thierry PINEAU;
Thierry PINEAU
3
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Jean GIRARD;
Jean GIRARD
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
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Jean-Paul PEGORIER
Jean-Paul PEGORIER
4
1Endocrinologie Métabolisme et Développement, CNRS UPR 1524, 9, rue Jules Hetzel, 92190 Meudon, France
4To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
September 13 2000
Revision Received:
November 13 2000
Accepted:
December 08 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 354 (1): 189–197.
Article history
Received:
September 13 2000
Revision Received:
November 13 2000
Accepted:
December 08 2000
Citation
Jean-Francç;ois LOUET, Florence CHATELAIN, Jean-Francç;ois DECAUX, Edwards A. PARK, Claude KOHL, Thierry PINEAU, Jean GIRARD, Jean-Paul PEGORIER; Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway. Biochem J 15 February 2001; 354 (1): 189–197. doi: https://doi.org/10.1042/bj3540189
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