Cited by 943Peroxisome Proliferator-Activated ReceptorsMetabolism and Genetic DisordersCancer, Lipids, and Metabolism

A critical role for the peroxisome proliferator-activated receptor α (PPARα) in the cellular fasting response: The PPARα-null mouse as a model of fatty acid oxidation disorders

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Leone, Teresa C., Weinheimer, Carla J., Kelly, Daniel P.·1999·Proceedings of the National Academy of Sciences

Abstract

We hypothesized that the lipid-activated transcription factor, the peroxisome proliferator-activated receptor alpha (PPARalpha), plays a pivotal role in the cellular metabolic response to fasting. Short-term starvation caused hepatic steatosis, myocardial lipid accumulation, and hypoglycemia, with an inadequate ketogenic response in adult mice lacking PPARalpha (PPARalpha-/-), a phenotype that bears remarkable similarity to that of humans with genetic defects in mitochondrial fatty acid oxidation enzymes. In PPARalpha+/+ mice, fasting induced the hepatic and cardiac expression of PPARalpha target genes encoding key mitochondrial (medium-chain acyl-CoA dehydrogenase, carnitine palmitoyltransferase I) and extramitochondrial (acyl-CoA oxidase, cytochrome P450 4A3) enzymes. In striking contrast, the hepatic and cardiac expression of most PPARalpha target genes was not induced by fasting in PPARalpha-/- mice. These results define a critical role for PPARalpha in a transcriptional regulatory response to fasting and identify the PPARalpha-/- mouse as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization.

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  • In response to fasting, the liver increases hepatic glucose production via glycogenolysis and gluconeogenesis to supply glucose as a fuel source for non-hepatic tissues including the brain and skeletal muscle.

    “In response to fasting, however, the liver increases hepatic glucose production via glycogenolysis and gluconeogenesis to supply glucose as a fuel source for non-hepatic tissues including the brain and skeletal muscle [15,16].”

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Research works printed but not linked: 6

  1. [3]Parvin R, Pande S V. J Biol Chem. 1979;254:5423–5429. [PubMed] [Google Scholar]
  2. [5]Nagao M, Parimoo B, Tanaka K. J Biol Chem. 1993;268:24114–24124. [PubMed] [Google Scholar]
  3. [13]Takeyama D, Kagaya Y, Yamane Y, Shiba N, Chida M, Takahashi T, Ido T, Ishide N, Takishima T. Cardiovasc Res. 1995;29:763–767. [PubMed] [Google Scholar]
  4. [21]Djouadi, F., Brandt, J., Weinheimer, C. J., Leone, T. C., Gonzalez, F. J. & Kelly, D. P. (1999) Prostaglandins Leukotrienes Essent. Fatty Acids, in press. [DOI] [PubMed]
  5. [25]Muerhoff A S, Griffin K J, Johnson E F. J Biol Chem. 1992;267:19051–19053. [PubMed] [Google Scholar]
  6. [34]Kelly D P, Gordon J I, Alpers R, Strauss A W. J Biol Chem. 1989;264:18921–18925. [PubMed] [Google Scholar]

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Authors
Leone, T. C., Weinheimer, C. J., & Kelly, D. P.
Affiliations
Washington University in St. Louis (US)
Venue
Proceedings of the National Academy of Sciences
Published
1999-06-22
Volume
96
Issue
13
Pages
7473-7478
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1975962309
Cited by
943
References
44
Citations by year
2026: 6 · 2025: 17 · 2024: 15 · 2023: 12 · 2022: 18 · 2021: 36 · 2020: 27 · 2019: 30 · 2018: 29 · 2017: 40 · 2016: 34 · 2015: 40 · 2014: 42 · 2013: 44 · 2012: 44
FWCI
11.66
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL58493, R01HL058493)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 45416, R01DK045416)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
PPARα, fasting response, fatty acid oxidation disorders, hepatic steatosis, myocardial lipid accumulation, hypoglycemia, ketogenesis, mitochondrial fatty acid oxidation, medium-chain acyl-CoA dehydrogenase, carnitine palmitoyltransferase 1, acyl-CoA oxidase, transcriptional regulation, lipid metabolism
MeSH terms
Animals, Carnitine O-Palmitoyltransferase, Cytochrome P-450 Enzyme System, Fasting, Fatty Acids, Humans, Liver, Myocardium, Nuclear Proteins, Oxidation-Reduction, Oxidoreductases, Transcription Factors, Gene Deletion, Receptors, Cytoplasmic and Nuclear, Acyl-CoA Oxidase, Acyl-CoA Dehydrogenase, Acyl-CoA Dehydrogenases, Lipid Metabolism, Mice

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