ArticleLipids in health and disease2024
Empagliflozin alleviates obesity-related cardiac dysfunction via the activation of SIRT3-mediated autophagosome formation.
Article in Lipids in health and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Empagliflozin Ameliorates Diabetic Cardiomyopathy by Inhibiting Ferroptosis via SIRT3: Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Article
- Empagliflozin Alleviates Osteoarthritis Progression by Attenuating Inflammation, Restoring Impaired Autophagy, and Ameliorating Chondrocyte Senescence.Biomedicines · 2026Article
- β-Asarone Attenuates Neuroinflammation of Alzheimer's Disease by Activating Autophagy and Suppressing NLRP3 Inflammasome Assembly.CNS neuroscience & therapeutics · 2026Article
- Empagliflozin in the Absence of Diabetes: A Systematic Review of Its Anthropometric and Metabolic Effects in Humans and Animals.International journal of endocrinology · 2026Article
- Sodium-glucose co-transporter inhibitors for APOL1 kidney disease: A call for studies.International urology and nephrology · 2025Review
- The landscape of novel antidiabetic drugs in diabetic HFpEF: relevant mechanisms and clinical implications.Cardiovascular diabetology · 2025Review
- Cardiometabolic Phenotype in HFpEF: Insights from Murine Models.Biomedicines · 2025Review
- Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- SIRT1: The first key to unlocking the mystery of cardiovascular diseases.Frontiers in pharmacology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundEmpagliflozin (EMPA) has demonstrated efficacy in providing cardiovascular benefits in metabolic diseases. However, the direct effect of EMPA on autophagy in obesity-related cardiac dysfunction remains unclear. Therefore, this study aimed to determine changes in cardiac autophagy during diet-induced obesity and clarify the exact mechanism by which EMPA regulates autophagic pathways.
methodsMale C57BL/6J mice were fed a 12-week high-fat diet (HFD) followed by 8 weeks of EMPA treatment. Body composition analysis and echocardiography were performed to evaluate metabolic alterations and cardiac function. Histological and immunofluorescence staining was used to evaluate potential enhancements in myocardial structure and biological function. Additionally, H9c2 cells were transfected with small interfering RNA targeting sirtuin 3 (SIRT3) and further treated with palmitic acid (PA) with or without EMPA. Autophagy-related targets were analyzed by western blotting and RT‒qPCR.
resultsEMPA administration effectively ameliorated metabolic disorders and cardiac diastolic dysfunction in HFD-fed mice. EMPA prevented obesity-induced myocardial hypertrophy, fibrosis, and inflammation through the activation of SIRT3-mediated autophagosome formation. The upregulation of SIRT3 triggered by EMPA promoted the initiation of autophagy by activating AMP-activated protein kinase (AMPK) and Beclin1. Furthermore, activated SIRT3 contributed to the elongation of autophagosomes through autophagy-related 4B cysteine peptidase (ATG4B) and autophagy-related 5 (ATG5).
conclusionsEMPA promotes SIRT3-mediated autophagosome formation to alleviate damage to the cardiac structure and function of obese mice. Activated SIRT3 initiates autophagy through AMPK/Beclin1 and further stimulates elongation of the autophagosome membrane via ATG4B/ATG5. These results provide a new explanation for the cardioprotective benefits of EMPA in obesity.
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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 Socratic graph.