Cited by 318Peroxisome Proliferator-Activated ReceptorsAdipose Tissue and MetabolismCancer, Lipids, and Metabolism

Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor

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Mascaró, Cristina, Acosta, Elena, Ortiz, José A., Marrero, Pedro F., Hegardt, Fausto G., Haro, Diego·1998·Journal of Biological Chemistry

Abstract

The expression of several genes involved in intra- and extracellular lipid metabolism, notably those involved in peroxisomal and mitochondrial beta-oxidation, is mediated by ligand-activated receptors, collectively referred to as peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of expression of carnitine palmitoyltransferase (CPT) genes, which are regulated by fatty acids, we have examined the transcriptional regulation of the human MCPT I gene. We have cloned by polymerase chain reaction the 5'-flanking region of this gene and demonstrated its transcriptional activity by transfection experiments with the CAT gene as a reporter. We have also shown that this is a target gene for the action of PPARs, and we have localized a PPAR responsive element upstream of the first exon. These results show that PPAR regulates the entry of fatty acids into the mitochondria, which is a crucial step in their metabolism, especially in tissues like heart, skeletal muscle and brown adipose tissue in which fatty acids are a major source of energy.

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  • Sensing of free fatty acid availability within the cell primarily occurs through peroxisome proliferator-activated receptors, which function as fatty acid-activated transcription factors that drive the expression of CPT1.

    “Sensing of free fatty acid availability within the cell primarily occurs through peroxisome proliferator–activated receptors, which function as fatty acid–activated transcription factors that drive the expression of CPT1 (64, 65).”
  • PPARα regulates peroxisomal and mitochondrial fatty acid β-oxidation.

    “Since PPARα regulates peroxisomal and mitochondrial fatty acid β-oxidation [59]”

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Research works printed but not linked: 3

  1. Forman, B. M., Chen, J., and Evans, R. M. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 4312-4317
  2. Kliewer, S. A., Sundseth, S. S., Jones, S. A., Broen, P. J., Wisely, G. B., Koble, C. S., Devchand, P., Wahli, W., Willson, T. M., Lenhard, J. M., and Lehmann, J. M. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 4318 -4323
  3. Gulick, T., Cresce, S., Caira, T., Moore, D. D., and Kelly, D. P. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 11012-11016

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Authors
Mascaró, C., Acosta, E., Ortiz, J. A., Marrero, P. F., Hegardt, F. G., & Haro, D.
Affiliations
Universitat de Barcelona (ES)
Corresponding author
Haro, Diego
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1998-04
Volume
273
Issue
15
Pages
8560-8563
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2080318925
Cited by
318
References
26
Citations by year
2025: 4 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 12 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 9 · 2012: 12
FWCI
7.09
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Universitat de Barcelona
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
carnitine palmitoyltransferase 1, peroxisome proliferator-activated receptors, gene transcription, 5'-flanking region, PPAR-responsive element, fatty acid beta-oxidation, skeletal muscle, gene cloning
MeSH terms
Animals, Base Sequence, Carnitine O-Palmitoyltransferase, Cell Line, Exons, Humans, Isoenzymes, Promoter Regions, Genetic, Recombinant Fusion Proteins, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcription, Genetic, Transfection, Chloramphenicol O-Acetyltransferase, Gene Expression Regulation, Enzymologic, Consensus Sequence, Sequence Alignment, Genes, Reporter, Receptors, Cytoplasmic and Nuclear, Muscle, Skeletal, Mice

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