ArticleFrontiers in pharmacology2021
Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Metabolic profiling of healthy vs. syndrome-associated obesity and effects of six-month metformin therapy.Acta diabetologica · 2026 · on this mapTrial
- 5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling.American journal of physiology. Cell physiology · 2026Article
- Intermittent fasting-induced autophagy normalization confers hepatic protection in metabolic dysfunction-associated fatty liver disease: Mechanistic insights and implications.Histology and histopathology · 2026Review
- The Role of Crosstalk Between the Unfolded Protein Response and Autophagy in Diseases Associated with Sympathetic Nervous System Imbalance: Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Pharmacological inhibition of G protein-coupled receptor kinase 5 decreases high-fat diet-induced hepatic steatosis in mice.Biochemical and biophysical research communications · 2026Article
- Induction of Autophagy as a Therapeutic Breakthrough for NAFLD: Current Evidence and Perspectives.Biology · 2025Review
- Targeting Lipophagy in Liver Diseases: Impact on Oxidative Stress and Steatohepatitis.Antioxidants (Basel, Switzerland) · 2025Review
- Ginsenoside CK and retinol on UVA-induced photoaging exert the synergistic effect through antioxidant and antiapoptotic mechanisms.Scientific reports · 2025Article
- Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats.Molecules (Basel, Switzerland) · 2025Article
- L-carnitine attenuates autophagic flux, apoptosis, and necroptosis in rats with dexamethasone-induced non-alcoholic steatohepatitis.BMC pharmacology & toxicology · 2024Article
- Metformin Protects Against Acute Kidney Injury Induced by Lipopolysaccharide via Up-Regulating the MCPIP1/SIRT1 Pathway.Biochemical genetics · 2024Article
- Empagliflozin add-on therapy is superior to metformin monotherapy in diabetic patients with NAFLD: An open-label, single-center, pilot clinical trial.Journal of general and family medicine · 2024Article
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?International journal of molecular sciences · 2024Review
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 2024Review
- Cell Death in Liver Disease and Liver Surgery.Biomedicines · 2024Review
- Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease.Autophagy · 2024Review
- The potential effect of metformin on fibroblast growth factor 21 in type 2 diabetes mellitus (T2DM).Inflammopharmacology · 2023Review
- mTOR-dependent TFEB activation and TFEB overexpression enhance autophagy-lysosome pathway and ameliorate Alzheimer's disease-like pathology in diabetic encephalopathy.Cell communication and signaling : CCS · 2023Article
- Mechanistic insights of soluble uric acid-induced insulin resistance: Insulin signaling and beyond.Reviews in endocrine & metabolic disorders · 2023Review
- Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease.Journal of cellular biochemistry · 2022Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.
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