Peroxisome Proliferator-Activated Receptor δ Is an Essential Transcriptional Regulator for Mitochondrial Protection and Biogenesis in Adult Heart

DOI Web Site 3 Citations
  • Peiyong Wang
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Jian Liu
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Yuquan Li
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Sijie Wu
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Jinwen Luo
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Huan Yang
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Ramasamy Subbiah
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • John Chatham
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Olga Zhelyabovska
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.
  • Qinglin Yang
    From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. Luo, H.Y., R.S., O.Z., Q.Y.); and Division of Cardiovascular Disease (J.C.), Department of Medicine, University of Alabama at Birmingham.

Description

<jats:p> <jats:bold> <jats:italic> <jats:underline>Rationale:</jats:underline> </jats:italic> </jats:bold> Peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ/β) are nuclear hormone receptors and ligand-activated transcription factors that serve as key determinants of myocardial fatty acid metabolism. Long-term cardiomyocyte-restricted PPARδ deficiency in mice leads to depressed myocardial fatty acid oxidation, bioenergetics, and premature death with lipotoxic cardiomyopathy. </jats:p> <jats:p> <jats:bold> <jats:italic> <jats:underline>Objective:</jats:underline> </jats:italic> </jats:bold> To explore the essential role of PPARδ in the adult heart. </jats:p> <jats:p> <jats:bold> <jats:italic> <jats:underline>Methods and Results:</jats:underline> </jats:italic> </jats:bold> We investigated the consequences of inducible short-term PPARδ knockout in the adult mouse heart. In addition to a substantial transcriptional downregulation of lipid metabolic proteins, short-term PPARδ knockout in the adult mouse heart attenuated cardiac expression of both Cu/Zn superoxide dismutase and manganese superoxide dismutase, leading to increased oxidative damage to the heart. Moreover, expression of key mitochondrial biogenesis determinants such as PPARγ coactivator-1 were substantially decreased in the short-term PPARδ deficient heart, concomitant with a decreased mitochondrial DNA copy number. Rates of palmitate and glucose oxidation were markedly depressed in cardiomyocytes of PPARδ knockout hearts. Consequently, PPARδ deficiency in the adult heart led to depressed cardiac performance and cardiac hypertrophy. </jats:p> <jats:p> <jats:bold> <jats:italic> <jats:underline>Conclusions:</jats:underline> </jats:italic> </jats:bold> PPARδ is an essential regulator of cardiac mitochondrial protection and biogenesis and PPARδ activation can be a potential therapeutic target for cardiac disorders. </jats:p>

Journal

  • Circulation Research

    Circulation Research 106 (5), 911-919, 2010-03-19

    Ovid Technologies (Wolters Kluwer Health)

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