ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Amyloid-Forming Amylin Secreted by the Pancreas Promotes Hypoxia-Inducible Factor Activation and Mitochondrial Alterations in Liver and Heart During Type 2 Diabetes Pathogenesis.Comprehensive physiology · 2026Article
- Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.Molecular and cellular biochemistry · 2025Review
- Dysregulated Fatty Acid Metabolism in Preeclampsia Among Highland Andeans: Insights Into Adaptive and Maladaptive Placental Metabolic Phenotypes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Placental mitochondria in high-altitude pregnancy: metabolic adaptations and a toolkit for respiratory assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Metabolic insights into hypoxia adaptation in adolescent athletes at different altitudes: a cross-sectional study.Frontiers in molecular biosciences · 2025Article
- Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond.Cardiovascular research · 2024Review
- Article
- Sex differences in metabolic adaptation in infants with cyanotic congenital heart disease.Pediatric research · 2024Article
- Alveolar hypoxia induces organ-specific inflammasome-related inflammation in male mouse lungs.Physiological reports · 2024Article
- HIF-1-Induced hsa-miR-429: Understanding Its Direct Targets as the Key to Developing Cancer Diagnostics and Therapies.Cancers · 2023Review
- Pathological implications of cellular stress in cardiovascular diseases.The international journal of biochemistry & cell biology · 2023Review
- CardiacHeart failure reviews · 2023Review
- Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling.Clinics (Sao Paulo, Brazil) · 2023Review
- Stearoyl-CoA Desaturase Regulates Angiogenesis and Energy Metabolism in Ischemic Cardiomyocytes.International journal of molecular sciences · 2022Article
- Regulatory miRNAs in Cardiovascular and Alzheimer's Disease: A Focus on Copper.International journal of molecular sciences · 2022Review
- Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation.Life (Basel, Switzerland) · 2022Review
- Intermittent Short-Duration Re-oxygenation Attenuates Cardiac Changes in Response to Hypoxia: Histological, Ultrastructural and Oxidant/Antioxidant Parameters.British journal of biomedical science · 2022Article
- Protective Roles of Apigenin Against Cardiometabolic Diseases: A Systematic Review.Frontiers in nutrition · 2022Review
- Effects of Altitude on the Digestion Performance, Serum Antioxidative Characteristics, Rumen Fermentation Parameters, and Rumen Bacteria of Sanhe Heifers.Frontiers in microbiology · 2022Article
- Metabolic Regulation of Cardiac Regeneration.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
The role of peroxisome proliferator-activated receptor α (PPARα)-mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 wk before in vivo contractile function was measured using cine MRI. In isolated, perfused hearts, energetics were measured using (31)P magnetic resonance spectroscopy (MRS), and glycolysis and fatty acid oxidation were measured using [(3)H] labeling. Compared with a normoxic, chow-fed control mouse heart, hypoxia decreased PPARα expression, fatty acid oxidation, and mitochondrial uncoupling protein 3 (UCP3) levels, while increasing glycolysis, all of which served to maintain normal ATP concentrations ([ATP]) and thereby, ejection fractions. A high-fat diet increased cardiac PPARα expression, fatty acid oxidation, and UCP3 levels with decreased glycolysis. Hypoxia was unable to alter the high PPARα expression or reverse the metabolic changes caused by the high-fat diet, with the result that [ATP] and contractile function decreased significantly. The adaptive metabolic changes caused by hypoxia in control mouse hearts were found to have occurred already in PPARα-deficient (PPARα(-/-)) mouse hearts and sustained function in hypoxia despite an inability for further metabolic remodeling. We conclude that decreased cardiac PPARα expression is essential for adaptive metabolic remodeling in hypoxia, but is prevented by dietary fat.-Cole, M. A., Abd Jamil, A. H., Heather, L. C., Murray, A. J., Sutton, E. R., Slingo, M., Sebag-Montefiore, L., Tan, S. C., Aksentijević, D., Gildea, O. S., Stuckey, D. J., Yeoh, K. K., Carr, C. A., Evans, R. D., Aasum, E., Schofield, C. J., Ratcliffe, P. J., Neubauer, S., Robbins, P. A., Clarke, K. On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.