Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway

J. F. Louet, F. Chatelain, J. F. Decaux, Edwards Park, C. Kohl, T. Pineau, J. Girard, J. P. Pegorier

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalBiochemical Journal
Volume354
Issue number1
DOIs
StatePublished - Feb 15 2001

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Carnitine O-Palmitoyltransferase
Peroxisome Proliferator-Activated Receptors
Gene expression
Liver
Fatty Acids
Genes
Gene Expression
Clofibrate
Lipids
Acyl Coenzyme A
Nucleic Acid Repetitive Sequences
Gene Expression Regulation
Mitochondrial Membranes
Metabolites
Cell culture
Knockout Mice
Introns
Hepatocytes
Esters
Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway. / Louet, J. F.; Chatelain, F.; Decaux, J. F.; Park, Edwards; Kohl, C.; Pineau, T.; Girard, J.; Pegorier, J. P.

In: Biochemical Journal, Vol. 354, No. 1, 15.02.2001, p. 189-197.

Research output: Contribution to journalArticle

Louet, J. F. ; Chatelain, F. ; Decaux, J. F. ; Park, Edwards ; Kohl, C. ; Pineau, T. ; Girard, J. ; Pegorier, J. P. / Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway. In: Biochemical Journal. 2001 ; Vol. 354, No. 1. pp. 189-197.
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