ArticleThe Journal of clinical investigation2010
PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidation.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 111 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
111 citing papers in PubMed, 155 citations in OpenAlex.
- The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.The Journal of clinical investigation · 2012Trial
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Intersecting Molecular Pathways in Cardiovascular Disease and Diabetes Mellitus: Emerging Roles of Inflammation and Therapeutics.Diabetes/metabolism research and reviews · 2026Review
- Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).International journal of molecular medicine · 2026Review
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- Seipin-Mediated Lipid Droplet Formation in Cardiomyocytes Ameliorates Cardiac Ischemia/Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The signaling pathway of PPAR-γ and its protective role in various diseases.Caspian journal of internal medicine · 2026Review
- Article
- Influence of diet-induced obesity and voluntary exercise training on cardiac lipids and mitochondrial function in mice.Journal of sport and health science · 2025Article
- OGT-mediated O-GlcNAc of FOXO1 promotes the progression of neonatal heart failure via regulating pyroptosis.Scientific reports · 2025Article
- FNDC4 Prevents Aging-Related Cardiac Dysfunction: By Restoring AMPKα/PPARα-Dependent Mitochondrial Function.JACC. Basic to translational science · 2025Article
- Empagliflozin in diabetic cardiomyopathy: elucidating mechanisms, therapeutic potentials, and future directions.Molecular biology reports · 2025Review
- The Protective Role of miR-130b-3p Against Palmitate-Induced Lipotoxicity in Cardiomyocytes Through PPARγ Pathway.International journal of molecular sciences · 2024Article
- Therapeutic potential of finerenone for diabetic cardiomyopathy: focus on the mechanisms.Diabetology & metabolic syndrome · 2024Review
- Cardiac Metabolism, Reprogramming, and Diseases.Journal of cardiovascular translational research · 2024Review
- Mechanism of Obesity-Related Lipotoxicity and Clinical Perspective.Advances in experimental medicine and biology · 2024Review
- Molecular Processes Involved in the Shared Pathways between Cardiovascular Diseases and Diabetes.Biomedicines · 2023Review
- Integrated Control of Fatty Acid Metabolism in Heart Failure.Metabolites · 2023Review
- The emergent role of mitochondrial surveillance in cellular health.Aging cell · 2022Review
- Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich's ataxia.Journal of lipid research · 2022Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Excess lipid accumulation in the heart is associated with decreased cardiac function in humans and in animal models. The reasons are unclear, but this is generally believed to result from either toxic effects of intracellular lipids or excessive fatty acid oxidation (FAO). PPARγ expression is increased in the hearts of humans with metabolic syndrome, and use of PPARγ agonists is associated with heart failure. Here, mice with dilated cardiomyopathy due to cardiomyocyte PPARγ overexpression were crossed with PPARα-deficient mice. Surprisingly, this cross led to enhanced expression of several PPAR-regulated genes that mediate fatty acid (FA) uptake/oxidation and triacylglycerol (TAG) synthesis. Although FA oxidation and TAG droplet size were increased, heart function was preserved and survival improved. There was no marked decrease in cardiac levels of triglyceride or the potentially toxic lipids diacylglycerol (DAG) and ceramide. However, long-chain FA coenzyme A (LCCoA) levels were increased, and acylcarnitine content was decreased. Activation of PKCα and PKCδ, apoptosis, ROS levels, and evidence of endoplasmic reticulum stress were also reduced. Thus, partitioning of lipid to storage and oxidation can reverse cardiolipotoxicity despite increased DAG and ceramide levels, suggesting a role for other toxic intermediates such as acylcarnitines in the toxic effects of lipid accumulation in the heart.
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What OpenQuestion holds
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.