Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor
Open accessAbstract
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).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [65]
PPARα regulates peroxisomal and mitochondrial fatty acid β-oxidation.
“Since PPARα regulates peroxisomal and mitochondrial fatty acid β-oxidation [59]”
From Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy (2019) · cites this paper as [59]
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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
- hybrid
- doi.org
- Licence
- 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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