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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
41
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pubmed:dateCreated |
2002-10-7
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pubmed:abstractText |
Liver carnitine palmitoyltransferase I catalyzes the transfer of long-chain fatty acids into mitochondria. L-CPT I is considered the rate-controlling enzyme in fatty acid oxidation. Expression of the L-CPT I gene is induced by starvation in response to glucagon secretion from the pancreas, an effect mediated by cAMP. Here, the molecular mechanisms underlying the induction of L-CPT I gene expression by cAMP were characterized. We demonstrate that the cAMP response unit of the L-CPT I gene is composed of a cAMP-response element motif and a DR1 sequence located 3 kb upstream of the transcription start site. Our data strongly suggest that the coactivator PGC-1 is involved in the regulation of this gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). Indeed, (i) cotransfection of CREB or HNF4 alpha dominant negative mutants completely abolishes the effect of cAMP on the L-CPT I promoter, and (ii) the cAMP-responsive unit binds HNF4 alpha and CREB through the DR1 and the cAMP-response element sequences, respectively. Moreover, cotransfection of PGC-1 strongly activates the L-CPT I promoter through HNF4 alpha bound at the DR1 element. Finally, we show that the transcriptional induction of the PGC-1 gene by glucagon through cAMP in hepatocytes precedes that of L-CPT-1. In addition to the key role that PGC-1 plays in glucose homeostasis, it may also be critical for lipid homeostasis. Taken together these observations suggest that PGC-1 acts to coordinate the process of metabolic adaptation in the liver.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/Carnitine O-Palmitoyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Hnf4a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hnf4a protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Tcfl4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/peroxisome-proliferator-activated...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37991-8000
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12107181-Animals,
pubmed-meshheading:12107181-Animals, Newborn,
pubmed-meshheading:12107181-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:12107181-Carnitine O-Palmitoyltransferase,
pubmed-meshheading:12107181-Cells, Cultured,
pubmed-meshheading:12107181-Cyclic AMP,
pubmed-meshheading:12107181-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:12107181-DNA-Binding Proteins,
pubmed-meshheading:12107181-Female,
pubmed-meshheading:12107181-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12107181-Genes, Reporter,
pubmed-meshheading:12107181-Glucagon,
pubmed-meshheading:12107181-Hepatocyte Nuclear Factor 4,
pubmed-meshheading:12107181-Hepatocytes,
pubmed-meshheading:12107181-Liver,
pubmed-meshheading:12107181-Mice,
pubmed-meshheading:12107181-Mice, Knockout,
pubmed-meshheading:12107181-Mutation,
pubmed-meshheading:12107181-Phosphoproteins,
pubmed-meshheading:12107181-Promoter Regions, Genetic,
pubmed-meshheading:12107181-Rats,
pubmed-meshheading:12107181-Rats, Wistar,
pubmed-meshheading:12107181-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12107181-Response Elements,
pubmed-meshheading:12107181-Transcription Factors
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pubmed:year |
2002
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pubmed:articleTitle |
The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB).
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pubmed:affiliation |
Institut Cochin, Département d'Endocrinologie, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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