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Review
. 2011 Mar;32(3):323-8.
doi: 10.1007/s00246-011-9889-8. Epub 2011 Feb 2.

Peroxisome proliferator activated receptor-alpha (PPARα) and PPAR gamma coactivator-1alpha (PGC-1α) regulation of cardiac metabolism in diabetes

Jennifer G Duncan  1
Affiliations
Review

Peroxisome proliferator activated receptor-alpha (PPARα) and PPAR gamma coactivator-1alpha (PGC-1α) regulation of cardiac metabolism in diabetes

Jennifer G Duncan. Pediatr Cardiol. 2011 Mar.

Abstract

Cardiovascular disease is a leading cause of mortality among patients with diabetes, and heart failure exists even in the absence of coronary disease. Myocardial metabolism is altered in the diabetic heart as a result of changes in substrate availability secondary to insulin resistance. The nuclear receptor peroxisome proliferator activated receptor-alpha (PPARα) and PPAR-gamma coactivator-1alpha (PGC-1α) play important roles in transcriptional regulation of myocardial metabolism and contribute significantly to the changes that occur in the diabetic heart. This review summarizes the role of PPARα and PGC-1α in myocardial metabolism in the normal heart and in the diabetic heart.

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Figures

Fig. 1
Fig. 1
Both peroxisome proliferator activated receptor-alpha (PPARα) and PPAR-gamma coactivator-1alpha (PGC-1α) are activated by insulin resistance and diabetes. Forming a heterodimer with RXRα, PPARα binds to a DNA response element, namely, the nuclear receptor response element (NRRE). At binding of the NRRE within the promoter of PPAR target genes, gene transcription is activated. The transcriptional activity of PPARα is influenced by binding of endogenous ligands and by the coactivator PGC-1α. Recruiting additional coactivators with histone acetyltransferase (HAT) activity, PGC-1α interacts with other regulators such as ménage-a-trois 1 (MAT) to promote chromatin remodeling and to facilitate gene transcription
See this image and copyright information in PMC

References

    1. Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005;1:259–271. - PubMed
    1. Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman BM. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPARγ coactivator 1α. Proc Natl Acad Sci USA. 2006;103:10086–10091. - PMC - PubMed
    1. Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP. Deactivation of peroxisome proliferator-activated receptor-α during cardiac hypertrophic growth. J Clin Invest. 2000;105:1723–1730. - PMC - PubMed
    1. Belke DD, Larsen TS, Gibbs EM, Severson DL. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am J Physiol Endocrinol Metab. 2000;279:E1104–E1113. - PubMed
    1. Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mecham RP, Kelly DP, Semenkovich CF. Dexamethasone induction of hypertension and diabetes is PPAR-α dependent in LDL receptor-null mice. Nat Med. 2003;9:1069–1075. - PubMed

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