ArticleJCI insight2019
Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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.
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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.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.Acta diabetologica · 2026Review
- Review Article: Targeting Peroxisome Proliferator-Activated Receptors in Primary Biliary Cholangitis.Alimentary pharmacology & therapeutics · 2026Review
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- Review
- Isolated mouse adult cardiomyocytes display minimal mitochondrial ATP demand and maximal reliance on glycolysis.Journal of molecular and cellular cardiology · 2025Article
- The transcription factor PPARA mediates SIRT1 regulation of NCOR1 to protect damaged heart cells.Cardiovascular diagnosis and therapy · 2024Article
- Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction.Cardiovascular diabetology · 2024Review
- Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway.Diabetes & metabolism journal · 2024Article
- Mitochondrial abnormality in ovarian granulosa cells of patients with polycystic ovary syndrome.Molecular medicine reports · 2024Article
- Addressing chemically-induced obesogenic metabolic disruption: selection of chemicals forFrontiers in endocrinology · 2024Review
- Beneficial effects of flavonoids on animal models of atherosclerosis: A systematic review and meta-analysis.iScience · 2023Article
- Calponin 2 regulates ketogenesis to mitigate acute kidney injury.JCI insight · 2023Article
- Can Resveratrol Influence the Activity of 11β-Hydroxysteroid Dehydrogenase Type 1? A Combined In Silico and In Vivo Study.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- Efficacy and Safety of Angiotensin Receptor Blockers in a Pre-Clinical Model of Arrhythmogenic Cardiomyopathy.International journal of molecular sciences · 2022Article
- The impact of diet upon mitochondrial physiology (Review).International journal of molecular medicine · 2022Review
- Sirtfoods: New Concept Foods, Functions, and Mechanisms.Foods (Basel, Switzerland) · 2022Review
- Protective effects and mechanisms of psoralidin against adriamycin-induced cardiotoxicity.Journal of advanced research · 2022Article
- Maternal obesity: influencing the heart right from the start.The Journal of physiology · 2022Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Dual peroxisome proliferator-activated receptor (PPAR)α/γ agonists that were developed to target hyperlipidemia and hyperglycemia in type 2 diabetes patients, caused cardiac dysfunction or other adverse effects. We studied the mechanisms that underlie the cardiotoxic effects of a dual PPARα/γ agonist, tesaglitazar, in wild type and diabetic (leptin receptor deficient - db/db) mice. Mice treated with tesaglitazar-containing chow or high fat diet developed cardiac dysfunction despite lower plasma triglycerides and glucose levels. Expression of cardiac peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which promotes mitochondrial biogenesis, had the most profound reduction among various fatty acid metabolism genes. Furthermore, we observed increased acetylation of PGC1α, which suggests PGC1α inhibition and lowered sirtuin 1 (SIRT1) expression. This change was associated with lower mitochondrial abundance. Combined pharmacological activation of PPARα and PPARγ in C57BL/6 mice reproduced the reduction of PGC1α expression and mitochondrial abundance. Resveratrol-mediated SIRT1 activation attenuated tesaglitazar-induced cardiac dysfunction and corrected myocardial mitochondrial respiration in C57BL/6 and diabetic mice but not in cardiomyocyte-specific Sirt1-/- mice. Our data shows that drugs, which activate both PPARα and PPARγ lead to cardiac dysfunction associated with PGC1α suppression and lower mitochondrial abundance likely due to competition between these two transcription factors.
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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.