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Regnault TR, Zhao L, Chiu JS, et al. Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism. PPAR Res. 2010;2010:129173doi: 10.1155/2010/129173.
Regnault, T. R., Zhao, L., Chiu, J. S., Gottheil, S. K., Foran, A., & Yee, S. P. (2010). Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism. PPAR research, 2010129173. https://doi.org/10.1155/2010/129173
Regnault, Timothy R H, et al. "Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism." PPAR research vol. 2010 (2010): 129173. doi: https://doi.org/10.1155/2010/129173
Regnault TR, Zhao L, Chiu JS, Gottheil SK, Foran A, Yee SP. Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism. PPAR Res. 2010;2010:129173. doi: 10.1155/2010/129173. Epub 2010 Nov 24. PMID: 21113404; PMCID: PMC2991640.
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PPAR Res. 2010;2010:129173. doi: 10.1155/2010/129173. Epub 2010 Nov 24.

Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism.

PPAR research

Timothy R H Regnault, Lin Zhao, Jacky S S Chiu, Stephanie K Gottheil, Allison Foran, Siu-Pok Yee

Affiliations

  1. Children's Health Research Institute and Lawson Research Institute, Department of Obstetrics and Gynecology, University of Western Ontario, London, ON, Canada N6A 5C1.

PMID: 21113404 PMCID: PMC2991640 DOI: 10.1155/2010/129173

Abstract

PPAR-α, PPAR-β, and PPAR-γ, and RXR in conjunction with PGC-1α and SIRT1, activate oxidative metabolism genes determining insulin sensitivity. In utero, hypoxia is commonly observed in Intrauterine Growth Restriction (IUGR), and reduced insulin sensitivity is often observed in these infants as adults. We sought to investigate how changes in oxygen tension might directly impact muscle PPAR regulation of oxidative genes. Following eight days in culture at 1% oxygen, C(2)C(12) muscle myoblasts displayed a reduction of PGC-1α, PPAR-α, and RXR-α mRNA, as well as CPT-1b and UCP-2 mRNA. SIRT1 and PGC-1α protein was reduced, and PPAR-γ protein increased. The addition of a PPAR-β agonist (L165,041) for the final 24 hours of 1% treatment resulted in increased levels of UCP-2 mRNA and protein whereas Rosiglitazone induced SIRT1, PGC-1α, RXR-α, PPAR-α, CPT-1b, and UCP-2 mRNA and SIRT1 protein. Under hypoxia, Resveratrol induced SIRT1, RXR-α, PPAR-α mRNA, and PPAR-γ and UCP-2 protein. These findings demonstrate that hypoxia alters the components of the PPAR pathway involved in muscle fatty acid oxidative gene transcription and translation. These results have implications for understanding selective hypoxia adaptation and how it might impact long-term muscle oxidative metabolism and insulin sensitivity.

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