ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild-type and β-carotene 9',10' oxygenase knockout mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 9 citations in OpenAlex.
- Review
- Amino acid insufficiency impairs hepatic vitamin A mobilization in mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Potential of Pumpkin Pulp Carotenoid Extract in the Prevention of Doxorubicin-Induced Cardiotoxicity.Pharmaceutics · 2025Article
- Acyl-CoA-binding protein as a driver of pathological aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Melatonin attenuates inflammatory bone loss by alleviating mitophagy and lactate production.Apoptosis : an international journal on programmed cell death · 2025Article
- Signaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations.Current topics in developmental biology · 2025Review
- Potential molecular and cellular mechanisms of the effects of cuproptosis-related genes in the cardiomyocytes of patients with diabetic heart failure: a bioinformatics analysis.Frontiers in endocrinology · 2024Article
- Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild-type and β-carotene 9',10' oxygenase knockout mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Regulation of the pyruvate dehydrogenase (PDH) complex by the pyruvate dehydrogenase kinase PDK4 enables the heart to respond to fluctuations in energy demands and substrate availability. Retinoic acid, the transcriptionally active form of vitamin A, is known to be involved in the regulation of cardiac function and growth during embryogenesis as well as under pathological conditions. Whether retinoic acid also maintains cardiac health under physiological conditions is unknown. However, vitamin A status and intake of its carotenoid precursor β-carotene have been linked to the prevention of heart diseases. Here, we provide in vitro and in vivo evidence that retinoic acid regulates cardiac Pdk4 expression and thus PDH activity. Furthermore, we show that mice lacking β-carotene 9',10'-oxygenase (BCO2), the only enzyme of the adult heart that cleaves β-carotene to generate retinoids (vitamin A and its derivatives), displayed cardiac retinoic acid insufficiency and impaired metabolic flexibility linked to a compromised PDK4/PDH pathway. These findings provide novel insights into the functions of retinoic acid in regulating energy metabolism in adult tissues, especially the heart.
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