{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:18:06Z","timestamp":1791415086049,"version":"4.3.3"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2007,4,17]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Transport rates of long-chain free fatty acids into mitochondria via carnitine palmitoyltransferase I relative to overall oxidative rates in hypertrophied hearts remain poorly understood. Furthermore, the extent of glucose oxidation, despite increased glycolysis in hypertrophy, remains controversial. The present study explores potential compensatory mechanisms to sustain tricarboxylic acid cycle flux that resolve the apparent discrepancy of reduced fatty acid oxidation without increased glucose oxidation through pyruvate dehydrogenase complex in the energy-poor, hypertrophied heart.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    We studied flux through the oxidative metabolism of intact adult rat hearts subjected to 10 weeks of pressure overload (hypertrophied; n=9) or sham operation (sham; n=8) using dynamic\n                    <jats:sup>13<\/jats:sup>\n                    C\u2013nuclear magnetic resonance. Isolated hearts were perfused with [2,4,6,8,10,12,14,16-\n                    <jats:sup>13<\/jats:sup>\n                    C\n                    <jats:sub>8<\/jats:sub>\n                    ] palmitate (0.4 mmol\/L) plus glucose (5 mmol\/L) in a 14.1-T nuclear magnetic resonance magnet. At similar tricarboxylic acid cycle rates, flux through carnitine palmitoyltransferase I was 23% lower in hypertrophied (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.04) compared with sham hearts and corresponded to a shift toward increased expression of the L\u2013carnitine palmitoyltransferase I isoform. Glucose oxidation via pyruvate dehydrogenase complex did not compensate for reduced palmitate oxidation rates. However, hypertrophied rats displayed an 83% increase in anaplerotic flux into the tricarboxylic acid cycle (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.03) that was supported by glycolytic pyruvate, coincident with increased mRNA transcript levels for malic enzyme.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In cardiac hypertrophy, fatty acid oxidation rates are reduced, whereas compensatory increases in anaplerosis maintain tricarboxylic acid cycle flux and account for a greater portion of glucose oxidation than previously recognized. The shift away from acetyl coenzyme A production toward carbon influx via anaplerosis bypasses energy, yielding reactions contributing to a less energy-efficient heart.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.106.668665","type":"journal-article","created":{"date-parts":[[2007,4,2]],"date-time":"2007-04-02T20:58:39Z","timestamp":1175547519000},"page":"2033-2041","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":176,"title":["Recruitment of Compensatory Pathways to Sustain Oxidative Flux With Reduced Carnitine Palmitoyltransferase I Activity Characterizes Inefficiency in Energy Metabolism in Hypertrophied Hearts"],"prefix":"10.1161","volume":"115","author":[{"given":"Natalia","family":"Sorokina","sequence":"first","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"McKinney","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla M.","family":"Pound","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gebre","family":"Woldegiorgis","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn F.","family":"LaNoue","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Ballal","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Taegtmeyer","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; Department of Environmental and Biomolecular Systems (G.W.), Oregon Health and Science University, Beaverton; Department of Molecular and Cellular Physiology (K.F.L.), Pennsylvania State University Medical School, Hershey; and Department of Internal Medicine (K.B., H.T...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Buttrick","sequence":"additional","affiliation":[{"name":"From the Program in Integrative Cardiac Metabolism (N.S., J.M.O., K.M.P., E.D.L.) and Center for Cardiovascular Research (N.S., J.M.O., R.D.M., K.M.P., P.M.B., E.D.L.), University of Illinois at Chicago, College of Medicine, Chicago; 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