ArticleJournal of advanced research2025
AdipoRon ameliorates the progression of heart failure with preserved ejection fraction via mitigating lipid accumulation and fibrosis.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Cardiac energy substrate utilization in heart failure with preserved ejection fraction: reconciling conflicting evidence on fatty acid and glucose metabolism.American journal of physiology. Heart and circulatory physiology · 2025Pooled it
- The effect of empagliflozin on peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction.Cardiovascular diabetology · 2025Trial
- 4-Octyl Itaconate Attenuates Age-Induced Parotid Gland Dysfunction Through the Suppression of Fibrosis and Lipid Deposition by AMPKα/PPARα and the Inhibition of Oxidative Stress via the AMPKα/Nrf2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Exerkines in precision management of metabolic diseases.Chinese medical journal · 2026Review
- Adiponectin receptor agonist AdipoRon induces autophagy via AdipoR1/2-AMPK pathway and suppresses tumor progression in ovarian cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Short-Chain Fatty Acids in Heart Failure with Preserved Ejection Fraction: Pathophysiological Roles and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Integrated Myocardial and Plasma Lipidome Across the Human Obesity-Heart Failure Spectrum.Research square · 2026Article
- Review
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
- CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.Journal of translational medicine · 2026Article
- The Regulatory Landscape of Ferroptosis and Iron Homeostasis: Pathophysiological Mechanisms and Therapeutic Horizons in Cardiovascular Disease.Drug design, development and therapy · 2026Review
- Cross-cutting circuits in heart failure with preserved ejection fraction: Integrating adipokine biology, mechanotransduction, and precision targeting.International journal of biological sciences · 2026Review
- Mitochondrial-inflammatory coupling in HFpEF: an emerging mechanistic framework for understanding the cardioprotective effects of SGLT2 inhibitors.Frontiers in cardiovascular medicine · 2026Review
- Article
- Adipocytokines as Pathogenic Mediators and Therapeutic Targets in Metabolic Syndrome-Related Cardiocerebrovascular Events.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Adiponectin Signaling Ameliorates Cognitive Dysfunction in Type 2 Diabetic Mice by Activating the Hippocampal AdipoR2-PPARα/CREB Pathway.Molecular neurobiology · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Review
- Porphyromonas gingivalis extracellular vesicles exacerbated osteoporosis by disrupting osteoblast mitochondrial dynamics and inhibiting Cpt2-regulated fatty acid oxidation.Journal of nanobiotechnology · 2025Article
- The Incremental Prognostic Value of Incorporating the Triglyceride-Glucose Index into the Traditional Cardiovascular Risk Factors for the Long-term Prognosis in Ischemic Cardiomyopathy Patients with HFpEF following Coronary Artery Bypass Grafting: A Multicenter Cohort Study.Journal of atherosclerosis and thrombosis · 2025Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionObesity and imbalance in lipid homeostasis contribute greatly to heart failure with preserved ejection fraction (HFpEF), the dominant form of heart failure. Few effective therapies exist to control metabolic alterations and lipid homeostasis.
objectivesWe aimed to investigate the cardioprotective roles of AdipoRon, the adiponectin receptor agonist, in regulating lipid accumulation in the two-hit HFpEF model.
methodsHFpEF mouse model was induced using 60 % high-fat diet plus L-NAME drinking water. Then, AdipoRon (50 mg/kg) or vehicle were administered by gavage to the two-hit HFpEF mouse model once daily for 4 weeks. Cardiac function was evaluated using echocardiography, and Postmortem analysis included RNA-sequencing, untargeted metabolomics, transmission electron microscopy and molecular biology methods.
resultsOur study presents the pioneering evidence that AdipoR was downregulated and impaired fatty acid oxidation in the myocardia of HFpEF mice, which was associated with lipid metabolism as indicated by untargeted metabolomics. AdipoRon, orally active synthetic adiponectin receptor agonist, could upregulate AdipoR1/2 (independently of adiponectin) and reduce lipid droplet accumulation, and alleviate fibrosis to restore HFpEF phenotypes. Finally, AdipoRon primarily exerted its effects through restoring the balance of myocardial fatty acid intake, transport, and oxidation via the downstream AMPKα or PPARα signaling pathways. The protective effects of AdipoRon in HFpEF mice were reversed by compound C and GW6471, inhibitors of AMPKα and PPARα, respectively.
conclusionsAdipoRon ameliorated the HFpEF phenotype by promoting myocardial fatty acid oxidation, decreasing fatty acid transport, and inhibiting fibrosis via the upregulation of AdipoR and the activation of AdipoR1/AMPKα and AdipoR2/PPARα-related downstream pathways. These findings underscore the therapeutic potential of AdipoRon in HFpEF. Importantly, all these parameters get restored in the context of continued mechanical and metabolic stressors associated with HFpEF.
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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.