ArticleScientific reports2015
Metformin inhibits hepatocellular glucose, lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2 (SRC-2).
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Meta-Analysis of Microarray Expression Studies on Metformin in Cancer Cell Lines.International journal of molecular sciences · 2019Pooled it
- Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets.Drug design, development and therapy · 2019Trial
- Methanimine derivative (BN3) alleviates obesity-associated neurobehavior alteration by influencing metabolic and neuroinflammatory gene pathways in in-vivo zebrafish model.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).Nutrition & metabolism · 2024Review
- SignalingProfiler 2.0 a network-based approach to bridge multi-omics data to phenotypic hallmarks.NPJ systems biology and applications · 2024Article
- Metformin and the Liver: Unlocking the Full Therapeutic Potential.Metabolites · 2024Review
- Olanzapine, risperidone and ziprasidone differently affect lysosomal function and autophagy, reflecting their different metabolic risk in patients.Translational psychiatry · 2024Article
- Metformin Inefficiency to Lower Lipids in Vitamin B12 Deficient HepG2 Cells Is Alleviated via Adiponectin-AMPK Axis.Nutrients · 2023Article
- Metformin-Induced Receptor Turnover Alters Antibody Accumulation in HER-Expressing Tumors.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- A pilot metabolomic study of drug interaction with the immune response to seasonal influenza vaccination.NPJ vaccines · 2023Article
- Metformin induces pyroptosis in leptin receptor-defective hepatocytes via overactivation of the AMPK axis.Cell death & disease · 2023Article
- The anti-diabetic effects of metformin are mediated by regulating long non-coding RNA.Frontiers in pharmacology · 2023Review
- A comparative evaluation of cardiac and neurological safety status of two commonly used oral hypoglycaemic agents in T2-DM Swiss albino mice model.Metabolism open · 2022Article
- Article
- Short-Term Metformin Treatment EnrichesFrontiers in microbiology · 2022Article
- Correlation between long-term use of metformin and incidence of NAFLD among patients with type 2 diabetes mellitus: A real-world cohort study.Frontiers in endocrinology · 2022Article
- Construction of a lipid metabolism-related and immune-associated prognostic signature for hepatocellular carcinoma.Cancer medicine · 2020Article
- Metabolic and transcriptome responses of RNAi-mediated AMPKα knockdown in Tribolium castaneum.BMC genomics · 2020Article
- Long-term treatment with metformin in the prevention of fatty liver in Zucker diabetic fatty rats.Diabetology & metabolic syndrome · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of the anti-diabetic drug metformin to inhibit anabolic processes including gluconeogenesis and lipogenesis is partly attributable to activation of the AMP-activated protein kinase (AMPK) pathway. The p160 steroid receptor coactivator 2 (SRC-2) is a key regulator of cellular metabolism and drives expression of the gluconeogenic enzyme glucose-6-phosphatase (G6Pc). Here, we uncovered a role for SRC-2 in the metabolic reprogramming imposed by metformin. In FaO cells, metformin dose-dependently reduced mRNA expression of SRC-2. Microarray analysis of metformin-treated cells revealed an overrepresentation of downregulated genes involved in biosynthesis of lipids and cholesterol. Several metformin-regulated genes including fatty acid synthase (FASN) were validated as transcriptional targets of SRC-2 with promoters characterized by sterol regulatory element (SRE) binding protein (SREBP) recognition sequences. Transactivation assays of the FASN promoter confirmed that SRC-2 is a coactivator of SREBP-1. By suppressing SRC-2 at the transcriptional level, metformin impeded recruitment of SRC-2 and RNA polymerase II to the G6Pc promoter and to SREs of mutual SRC-2/SREBP-1 target gene promoters. Hepatocellular fat accretion was reduced by metformin or knock-down of both SRC-2 and SREBP-1. Accordingly we propose that metformin inhibits glucose and lipid biosynthesis partly by downregulating SRC-2 gene expression.
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