{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:00:48Z","timestamp":1791846048226,"version":"4.3.4"},"reference-count":68,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,1,22]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Fatty acid oxidation is transcriptionally regulated by peroxisome proliferator\u2013activated receptor (PPAR)\u03b1 and under normal conditions accounts for 70% of cardiac ATP content. Reduced\n              <jats:italic>Ppara<\/jats:italic>\n              expression during sepsis and heart failure leads to reduced fatty acid oxidation and myocardial energy deficiency. Many of the transcriptional regulators of\n              <jats:italic>Ppara<\/jats:italic>\n              are unknown.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              To determine the role of Kr\u00fcppel-like factor 5 (KLF5) in transcriptional regulation of\n              <jats:italic>Ppara<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We discovered that KLF5 activates\n              <jats:italic>Ppara<\/jats:italic>\n              gene expression via direct promoter binding. This is blocked in hearts of septic mice by c-Jun, which binds an overlapping site on the\n              <jats:italic>Ppara<\/jats:italic>\n              promoter and reduces transcription. We generated cardiac myocyte\u2013specific\n              <jats:italic>Klf5<\/jats:italic>\n              knockout mice that showed reduced expression of cardiac\n              <jats:italic>Ppara<\/jats:italic>\n              and its downstream fatty acid metabolism\u2013related targets. These changes were associated with reduced cardiac fatty acid oxidation, ATP levels, increased triglyceride accumulation, and cardiac dysfunction. Diabetic mice showed parallel changes in cardiac\n              <jats:italic>Klf5<\/jats:italic>\n              and\n              <jats:italic>Ppara<\/jats:italic>\n              expression levels.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Cardiac myocyte KLF5 is a transcriptional regulator of\n              <jats:italic>Ppara<\/jats:italic>\n              and cardiac energetics.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.115.306383","type":"journal-article","created":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T03:13:24Z","timestamp":1447730004000},"page":"241-253","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["Cardiac Myocyte KLF5 Regulates\n            <i>Ppara<\/i>\n            Expression and Cardiac Function"],"prefix":"10.1161","volume":"118","author":[{"given":"Konstantinos","family":"Drosatos","sequence":"first","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina M.","family":"Pollak","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J.","family":"Pol","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Ntziachristos","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Willecke","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mesele-Christina","family":"Valenti","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad M.","family":"Trent","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunying","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaodong","family":"Guo","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iannis","family":"Aifantis","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira J.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"From the Metabolic Biology Laboratory, Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (K.D., C.J.P., M.-C.V.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (N.M.P.); Howard Hughes Medical Institute, Department of Pathology, New York University School of Medicine (P.N., I.A.); Division of Endocrinology, Diabetes, and Metabolism, New York University-Langone School of Medicine (F.W., C.M.T., Y.H., I.J.G.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00006.2004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001469"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra063052"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.08.015"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.272146"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.112.000177"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.110.959833"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.03.021"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2439"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.011687"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00058.2009"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210859200"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01942-07"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1797-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.02.001"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500463200"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410515200"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.024"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.531384"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121060109"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm738"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40295"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1756"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.021964"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.2979"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.04.008"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5298.400"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-13-0327"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207837200"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0938"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00088.2010"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.61"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0259"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.02.001"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.11.010"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI14080"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.09.030"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/253817"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.060889"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2009"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2004.11.005"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn001"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl014"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/652097"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.07.150"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800147-JLR200"},{"key":"e_1_3_4_48_2","first-page":"81","article-title":"Idiopathic dilated cardiomyopathy\u2013an evidence of abnormal lipid accumulation accumulation in myocardium.","volume":"3","author":"Tomita T","year":"1990","unstructured":"Tomita T, Wilson L, Chiga M. 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