ArticleThe Journal of clinical investigation2002
The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 454 papers.
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Who cites it
454 citing papers in PubMed, 876 citations in OpenAlex.
- Alterations in plasma triglycerides and ceramides: links with cardiac function in humans with type 2 diabetes.Journal of lipid research · 2020Trial
- A muscle-enriched mitochondrial protein regulates postnatal heart growth through mitonuclear ubiquinone-PPAR signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PERM1 Gene Therapy Prevents Pressure Overload-induced Heart Failure Through a Sarcomere-Mitochondria Energetic Microdomain.Research square · 2026Article
- Substrate-specific mitochondrial dysfunction and metabolomic profiles in type 2 diabetic rat hearts.Experimental physiology · 2026Article
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Cluster of Differentiation 36-Mediated Inflammation and Lipid Metabolism in Cardiovascular Diseases: From Mechanisms to Novel Therapies.Antioxidants (Basel, Switzerland) · 2026Review
- PPARα: Linking Cardiac Metabolism to Therapeutic Opportunities in Cardiovascular Diseases.Cells · 2026Review
- Peroxisome proliferator-activated receptor-α activation attenuates susceptibility to postoperative atrial fibrillation.Journal of thoracic disease · 2026Article
- Regulation of mitochondrial biogenesis and energy metabolism in the heart.Chinese medical journal · 2026Review
- Sodium-glucose Co-transporter 2 (SGLT2) inhibitor dapagliflozin acutely activates cardiomyocyte HIF-1α signaling via succinate, a signaling metabolite.Journal of pharmacological sciences · 2026Article
- Peroxisome proliferator‑activated receptor α regulates acesulfame‑K‑induced NAFLD via hepatic PLCβ: Foe and friend.International journal of molecular medicine · 2026Article
- PPARα-NF-κB heterodimer mediates obesity-induced diastolic dysfunction through autocrine production of IL-6.The Journal of clinical investigation · 2026Article
- Lipotoxicity in Diabetic Cardiomyopathy: Molecular Basis and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Integrative insights into fatty acid metabolism in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies.iScience · 2026Review
- From kidney injury to cardiac dysfunction: the central role of oxidative stress in diabetes and CKD.Basic research in cardiology · 2026Article
- Diabetic cardiomyopathy as a disorder of proteostatic maladaptation: context-dependent ubiquitin-specific protease networks.Frontiers in cell and developmental biology · 2026Review
- The role of Western diet and gut microbiota in the pathogenesis of cardiovascular diseases.Frontiers in microbiology · 2026Review
- Sustained HIF activation in adult cardiomyocytes show transient beneficial effect in murine HFpEF model.European heart journal open · 2026Article
- Review
- A Molecular Perspective on the Intricate Interplay Among Exosomes, Bioenergetic Metabolism, and the Pathogenesis of Diabetic Cardiomyopathy.Journal of cardiovascular translational research · 2025Review
394 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Recent evidence has defined an important role for PPARalpha in the transcriptional control of cardiac energy metabolism. To investigate the role of PPARalpha in the genesis of the metabolic and functional derangements of diabetic cardiomyopathy, mice with cardiac-restricted overexpression of PPARalpha (MHC-PPAR) were produced and characterized. The expression of PPARalpha target genes involved in cardiac fatty acid uptake and oxidation pathways was increased in MHC-PPAR mice. Surprisingly, the expression of genes involved in glucose transport and utilization was reciprocally repressed in MHC-PPAR hearts. Consistent with the gene expression profile, myocardial fatty acid oxidation rates were increased and glucose uptake and oxidation decreased in MHC-PPAR mice, a metabolic phenotype strikingly similar to that of the diabetic heart. MHC-PPAR hearts exhibited signatures of diabetic cardiomyopathy including ventricular hypertrophy, activation of gene markers of pathologic hypertrophic growth, and transgene expression-dependent alteration in systolic ventricular dysfunction. These results demonstrate that (a) PPARalpha is a critical regulator of myocardial fatty acid uptake and utilization, (b) activation of cardiac PPARalpha regulatory pathways results in a reciprocal repression of glucose uptake and utilization pathways, and (c) derangements in myocardial energy metabolism typical of the diabetic heart can become maladaptive, leading to cardiomyopathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.