ArticleThe Journal of clinical investigation2007
Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
162 citing papers in PubMed, 2 syntheses or guidelines pooled it, 278 citations in OpenAlex.
- Metabolic Remodeling in the Pressure-Loaded Right Ventricle: Shifts in Glucose and Fatty Acid Metabolism-A Systematic Review and Meta-Analysis.Journal of the American Heart Association · 2019Pooled it
- Metabolic remodeling of substrate utilization during heart failure progression.Heart failure reviews · 2019Pooled it
- 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
- Lipid droplet-associated proteins: Roles in cardiovascular diseases.Journal of lipid research · 2026Review
- Qianyang Yuyin granule modulates glycolysis and inflammatory response to treat hypertensive cardiac remodeling.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Lipotoxicity in Diabetic Cardiomyopathy: Molecular Basis and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- The role of Western diet and gut microbiota in the pathogenesis of cardiovascular diseases.Frontiers in microbiology · 2026Review
- PPAR-δ is a potential modulator of central carbon metabolism in human adipocytes.Bioinformation · 2026Article
- A comprehensive review on diabetic cardiomyopathy (DCM): histological spectrum, diagnosis, pathogenesis, and management with conventional treatments and natural compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Molecular Mediators of the Cardiac Benefits of Exercise.Circulation research · 2025Review
- Cardiac ischaemia/reperfusion in pigs and mice increases cardiomyocyte Krüppel-like factor 5 that aggravates tissue injury and remodelling.Cardiovascular research · 2025Article
- Long Non-coding RNA Involved in the Pathophysiology of Atrial Fibrillation.Cardiovascular drugs and therapy · 2025Review
- Mitochondrial Dysfunction: A Roadmap for Understanding and Tackling Cardiovascular Aging.Aging and disease · 2024Review
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Cardiac Metabolism, Reprogramming, and Diseases.Journal of cardiovascular translational research · 2024Review
- Cardiac maturation.Journal of molecular and cellular cardiology · 2024Review
- Coordinated transcriptional upregulation of oxidative metabolism proteins in long-lived endocrine mutant mice.GeroScience · 2023Article
- Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration.Cellular and molecular life sciences : CMLS · 2023Review
- The 16α-hydroxylated Bile Acid, Pythocholic Acid Decreases Food Intake and Increases Oleoylethanolamide in Male Mice.Endocrinology · 2023Article
- Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions.Cell death discovery · 2023Review
102 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
9 authors at 2 institutions in 2 countries.
Funding
Abstract
In the diabetic heart, chronic activation of the PPARalpha pathway drives excessive fatty acid (FA) oxidation, lipid accumulation, reduced glucose utilization, and cardiomyopathy. The related nuclear receptor, PPARbeta/delta, is also highly expressed in the heart, yet its function has not been fully delineated. To address its role in myocardial metabolism, we generated transgenic mice with cardiac-specific expression of PPARbeta/delta, driven by the myosin heavy chain (MHC-PPARbeta/delta mice). In striking contrast to MHC-PPARalpha mice, MHC-PPARbeta/delta mice had increased myocardial glucose utilization, did not accumulate myocardial lipid, and had normal cardiac function. Consistent with these observed metabolic phenotypes, we found that expression of genes involved in cellular FA transport were activated by PPARalpha but not by PPARbeta/delta. Conversely, cardiac glucose transport and glycolytic genes were activated in MHC-PPARbeta/delta mice, but repressed in MHC-PPARalpha mice. In reporter assays, we showed that PPARbeta/delta and PPARalpha exerted differential transcriptional control of the GLUT4 promoter, which may explain the observed isotype-specific effects on glucose uptake. Furthermore, myocardial injury due to ischemia/reperfusion injury was significantly reduced in the MHC-PPARbeta/delta mice compared with control or MHC-PPARalpha mice, consistent with an increased capacity for myocardial glucose utilization. These results demonstrate that PPARalpha and PPARbeta/delta drive distinct cardiac metabolic regulatory programs and identify PPARbeta/delta as a potential target for metabolic modulation therapy aimed at cardiac dysfunction caused by diabetes and ischemia.
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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.