ArticleCirculation research2016
Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function.
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Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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82citing papers in PubMed, 1 pooled it
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Metabolic remodeling of substrate utilization during heart failure progression.Heart failure reviews · 2019Pooled it
- KLF5 Downregulation Links Impaired BNIP3-Mediated Mitophagy to Inflammatory Valve Remodeling in Calcific Aortic Valve Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Assessment of triglyceride-glucose composite indices associated mortality risk in diabetes-related heart failure.Journal of diabetes investigation · 2026Article
- KLF5-driven TAZ-FASN signaling reprograms fatty acid metabolism to support Treg differentiation in lung cancer.Journal of translational medicine · 2026Article
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Fatty Acids and Their Roles in Cardiac Physiology and Pathology: Mechanistic and Interventional Studies.Nutrients · 2026Review
- PPARα-NF-κB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6.The Journal of clinical investigation · 2026Article
- Targeting the undruggable transcription factor, KLF5, with a peptidomimetic small molecule, NC114, attenuates pressure overload-induced cardiac remodeling and fibrosis.Scientific reports · 2026Article
- FNDC4 Prevents Aging-Related Cardiac Dysfunction: By Restoring AMPKα/PPARα-Dependent Mitochondrial Function.JACC. Basic to translational science · 2025Article
- Cardiac ischaemia/reperfusion in pigs and mice increases cardiomyocyte Krüppel-like factor 5 that aggravates tissue injury and remodelling.Cardiovascular research · 2025Article
- Krüppel-like factor 5 remodels lipid metabolism in exercised skeletal muscle.Molecular metabolism · 2025Article
- Valerenic acid attenuates pathological myocardial hypertrophy by promoting the utilization of multiple substrates in the mitochondrial energy metabolism.Journal of advanced research · 2025Article
- Empagliflozin's cardioenergetic protective effects through PPARα pathway modulation in heart failure.Frontiers in pharmacology · 2025Article
- The transcription factor PPARA mediates SIRT1 regulation of NCOR1 to protect damaged heart cells.Cardiovascular diagnosis and therapy · 2024Article
- Daucosterol alleviates heart failure with preserved ejection fraction through activating PPARHeliyon · 2024Article
- Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions.International journal of molecular sciences · 2024Review
- Intermedin Alleviates Diabetic Cardiomyopathy by Up-Regulating CPT-1β through Activation of the Phosphatidyl Inositol 3 Kinase/Protein Kinase B Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Krüppel-like factors family in health and disease.MedComm · 2024Review
- 4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.Journal of orthopaedic surgery and research · 2024Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Konstantinos DrosatosFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.). drosatos@temple.edu.
Nina M PollakFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Christine J PolFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Panagiotis NtziachristosFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Florian WilleckeFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Mesele-Christina ValentiFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Chad M TrentFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Yunying HuFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Shaodong GuoFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Iannis AifantisFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Ira J GoldbergFrom 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.); and Division of Molecular Cardiology, Department of Medicine, Texas A & M Health Science Center, Temple (S.G.).
Howard Hughes Medical Institute · USNew York University · USUniversity of Graz · AT
Funding
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7MPathways of Tissue Lipid UptakeR01HL045095 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ABUMRAD, NADA A., GOLDBERG, IRA J · 1991 to 2024
$6.9MMechanisms of Fatty Acid Uptake By Cardiac MuscleR01HL073029 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GOLDBERG, IRA J · 2003 to 2021
$6.8MEXTRACELLULAR REGULATION OF LIPOPROTEIN LIPASE ACTIVITYR37HL045095 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GOLDBERG, IRA J · 2000 to 2009
$4.6MMechanisms of Reduced Fatty Acid Oxidation and Cardiac Dysfunction in SepsisR00HL112853 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI DROSATOS, KONSTANTINOS · 2014 to 2016
$725kMechanisms of Reduced Fatty Acid Oxidation and Cardiac Dysfunction in SepsisK99HL112853 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DROSATOS, KONSTANTINOS · 2012 to 2013
$268kExploring a new therapeutic approach through targeting epigenetic enzymes in ALLK99CA188293 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI NTZIACHRISTOS, PANAGIOTIS · 2014 to 2014
$90kAustrian Science Fund FWF W 1226NCI NIH HHS K99 CA188293NHLBI NIH HHS HL112853NHLBI NIH HHS HL45095NHLBI NIH HHS HL73029NHLBI NIH HHS K99 HL112853NHLBI NIH HHS R00 HL112853NHLBI NIH HHS R01 HL045095NHLBI NIH HHS R01 HL073029NHLBI NIH HHS R37 HL045095NIDDK NIH HHS P30 DK020541
Abstract
rationaleFatty acid oxidation is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)α and under normal conditions accounts for 70% of cardiac ATP content. Reduced Ppara expression during sepsis and heart failure leads to reduced fatty acid oxidation and myocardial energy deficiency. Many of the transcriptional regulators of Ppara are unknown.
objectiveTo determine the role of Krüppel-like factor 5 (KLF5) in transcriptional regulation of Ppara. METHODS AND
resultsWe discovered that KLF5 activates Ppara gene expression via direct promoter binding. This is blocked in hearts of septic mice by c-Jun, which binds an overlapping site on the Ppara promoter and reduces transcription. We generated cardiac myocyte-specific Klf5 knockout mice that showed reduced expression of cardiac Ppara and its downstream fatty acid metabolism-related 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 Klf5 and Ppara expression levels.
conclusionsCardiac myocyte KLF5 is a transcriptional regulator of Ppara and cardiac energetics.
Indexed as
Energy MetabolismAnimalsBinding, CompetitiveBinding SitesCardiomyopathy, DilatedCell LineDiabetes Mellitus, ExperimentalFatty AcidsGenotypeKruppel-Like Transcription FactorsMice, Inbred C57BLMice, KnockoutMyocytes, CardiacOxidation-ReductionPhenotypePPAR alphaFatty AcidsKlf5 protein, mouseKruppel-Like Transcription FactorsPPAR alphaProto-Oncogene Proteins c-junSlc5a2 protein, mouseSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsTriglyceridescardiac myocytefatty acidsheartheart failurePPAR alpha
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