ArticleCell death & disease2023
Metformin induces pyroptosis in leptin receptor-defective hepatocytes via overactivation of the AMPK axis.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting pyroptosis in metabolic dysfunction-associated steatotic liver disease: from molecular mechanisms to therapeutic innovation.Molecular biology reports · 2026Review
- Injectable photothermal hydrogel enables gas therapy to induce pyroptosis in colon tumors.Mikrochimica acta · 2025Article
- Targeting Ras homolog enriched in brain 1 to restore β-cell mass and function: A potential therapeutic strategy for diabetes.World journal of diabetes · 2025Article
- Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.Cell death discovery · 2025Review
- Multi-miRNAs-Mediated Hepatic Lepr Axis Suppression: A Pparg-Dicer1 Pathway-Driven Mechanism in Spermatogenesis for the Intergenerational Transmission of Paternal Metabolic Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.Frontiers in oncology · 2025Review
- Research progress on AMPK in the pathogenesis and treatment of MASLD.Frontiers in immunology · 2025Review
- Ferroptosis and pyroptosis in diabetes mellitus: emerging therapeutic potential of GLP-1 receptor agonists.Frontiers in clinical diabetes and healthcare · 2025Review
- Role of AMPKZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Evidence That Peripheral Leptin Resistance in Omental Adipose Tissue and Liver Correlates with MASLD in Humans.International journal of molecular sciences · 2024Article
- Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies.Chinese medicine · 2024Review
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Leptin receptor deficiency impedes metabolic surgery related-weight loss through inhibition of energy expenditure in db/db mice.Diabetology & metabolic syndrome · 2024Article
- Gasdermin D-Mediated Pyroptosis in Diabetic Cardiomyopathy: Molecular Mechanisms and Pharmacological Implications.Molecules (Basel, Switzerland) · 2023Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is the biguanide of hepatic insulin sensitizer for patients with non-alcohol fatty liver disease (NAFLD). Findings regarding its efficacy in restoring blood lipids and liver histology have been contradictory. In this study, we explore metformin's preventive effects on NAFLD in leptin-insensitive individuals. We used liver tissue, serum exosomes and isolated hepatocytes from high-fat diet (HFD)-induced Zucker diabetic fatty (ZDF) rats and leptin receptor (Lepr) knockout rats to investigate the correlation between hepatic Lepr defective and liver damage caused by metformin. Through immunostaining, RT-PCR and glucose uptake monitoring, we showed that metformin treatment activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream cytochrome C oxidase (CCO). This leads to overactivation of glucose catabolism-related genes, excessive energy repertoire consumption, and subsequent hepatocyte pyroptosis. Single-cell RNA sequencing further confirmed the hyper-activation of glucose catabolism after metformin treatment. Altogether, we showed that functional Lepr is necessary for metformin treatment to be effective, and that long-term metformin treatment might promote NAFLD progression in leptin-insensitive individuals. This provides important insight into the clinical application of metformin.
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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 OpenQuestion graph.