{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:39:34Z","timestamp":1791355174368,"version":"4.3.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,3,19]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale:<\/jats:underline>\n              <\/jats:italic>\n            <\/jats:bold>\n            Peroxisome proliferator-activated receptors (PPARs) (\u03b1, \u03b3, and \u03b4\/\u03b2) are nuclear hormone receptors and ligand-activated transcription factors that serve as key determinants of myocardial fatty acid metabolism. Long-term cardiomyocyte-restricted PPAR\u03b4 deficiency in mice leads to depressed myocardial fatty acid oxidation, bioenergetics, and premature death with lipotoxic cardiomyopathy.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective:<\/jats:underline>\n              <\/jats:italic>\n            <\/jats:bold>\n            To explore the essential role of PPAR\u03b4 in the adult heart.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results:<\/jats:underline>\n              <\/jats:italic>\n            <\/jats:bold>\n            We investigated the consequences of inducible short-term PPAR\u03b4 knockout in the adult mouse heart. In addition to a substantial transcriptional downregulation of lipid metabolic proteins, short-term PPAR\u03b4 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 PPAR\u03b3 coactivator-1 were substantially decreased in the short-term PPAR\u03b4 deficient heart, concomitant with a decreased mitochondrial DNA copy number. Rates of palmitate and glucose oxidation were markedly depressed in cardiomyocytes of PPAR\u03b4 knockout hearts. Consequently, PPAR\u03b4 deficiency in the adult heart led to depressed cardiac performance and cardiac hypertrophy.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions:<\/jats:underline>\n              <\/jats:italic>\n            <\/jats:bold>\n            PPAR\u03b4 is an essential regulator of cardiac mitochondrial protection and biogenesis and PPAR\u03b4 activation can be a potential therapeutic target for cardiac disorders.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.206185","type":"journal-article","created":{"date-parts":[[2010,1,15]],"date-time":"2010-01-15T02:09:35Z","timestamp":1263521375000},"page":"911-919","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Peroxisome Proliferator-Activated Receptor \u03b4 Is an Essential Transcriptional Regulator for Mitochondrial Protection and Biogenesis in Adult Heart"],"prefix":"10.1161","volume":"106","author":[{"given":"Peiyong","family":"Wang","sequence":"first","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Li","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijie","family":"Wu","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Luo","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"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."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramasamy","family":"Subbiah","sequence":"additional","affiliation":[{"name":"From the Department of Nutrition Sciences (P.W., J. Liu, Y.L., S.W., J. 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