ArticleJournal of the American Society of Nephrology : JASN2018
Phosphorylation of Acetyl-CoA Carboxylase by AMPK Reduces Renal Fibrosis and Is Essential for the Anti-Fibrotic Effect of Metformin.
Article in Journal of the American Society of Nephrology : JASN, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Metformin in non-diabetic patients with autosomal dominant polycystic kidney disease: a systematic review and meta-analysis of randomized controlled trials.BMC nephrology · 2025Pooled it
- Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2022Trial
- Lysophosphatidic acid promotes lipid metabolism through AMPK signaling to support Coxsackievirus infection.Journal of virology · 2026Article
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Dehydration promotes intracellular lipid synthesis and accumulation.Nature communications · 2026Article
- Metformin-induced xerostomia and chapped lips in a 56-year-old patient with early-stage diabetes: a case report.Journal of medical case reports · 2026Article
- Intratumoral microbiota promote pancreatic cancer progression via NaAc-mediated activation of the GPR43/AMPK/HADH pathway.Journal of translational medicine · 2026Article
- Citrate-Dependent Activation of Acetyl CoA Carboxylase Promotes Renal Lipid Accumulation in a Rat Model of Chronic Kidney Disease.Acta physiologica (Oxford, England) · 2026Article
- Modulation of the gut-heart axis by exercise in diabetic cardiomyopathy: Microbial mechanisms and clinical implications.iScience · 2026Review
- Comparative study of cardio-protective effect of metformin versus dapagliflozin in experimentally induced myocardial infarction in diabetic rats.BMC pharmacology & toxicology · 2026Article
- ND-630, an acetyl-CoA carboxylase inhibitor, prevents renal fibrosis in adenine-induced CKD mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Microproteins in Metabolic Biology: Emerging Functions and Potential Roles as Nutrient-Linked Biomarkers.International journal of molecular sciences · 2025Review
- The metformin mediated MAPK signaling pathway influences D-Xylose regulation during diabetic kidney disease therapy.Communications medicine · 2025Article
- Endoplasmic reticulum-mediated organelle crosstalk in kidney disease.Nature reviews. Nephrology · 2025Review
- The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study.Cardiovascular diabetology · 2025 · on this mapObservational
- G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy.Molecular biomedicine · 2025Article
- ACOT12, a novel factor in the pathogenesis of kidney fibrosis, modulates ACBD5.Experimental & molecular medicine · 2025Article
- Metabolite pathway alterations identified by magnetic resonance metabolomics in a proximal tubular epithelial cell line treated with TGF-β1.Physiological reports · 2025Article
- Metformin in gestational diabetes: physiological actions and clinical applications.Nature reviews. Endocrinology · 2025Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExpression of genes regulating fatty acid metabolism is reduced in tubular epithelial cells from kidneys with tubulointerstitial fibrosis (TIF), thus decreasing the energy produced by fatty acid oxidation (FAO). Acetyl-CoA carboxylase (ACC), a target for the energy-sensing AMP-activating protein kinase (AMPK), is the major controller of the rate of FAO within cells. Metformin has a well described antifibrotic effect, and increases phosphorylation of ACC by AMPK, thereby increasing FAO.
methodsWe evaluated phosphorylation of ACC in cell and mouse nephropathy models, as well as the effects of metformin administration in mice with and without mutations that reduce ACC phosphorylation.
resultsReduced phosphorylation of ACC on the AMPK site Ser79 occurred in both tubular epithelial cells treated with folate to mimic cellular injury and in wild-type (WT) mice after induction of the folic acid nephropathy model. When this effect was exaggerated in mice with knock-in (KI) Ser to Ala mutations of the phosphorylation sites in ACC, lipid accumulation and fibrosis increased significantly compared with WT. The effect of ACC phosphorylation on fibrosis was confirmed in the unilateral ureteric obstruction model, which showed significantly increased lipid accumulation and fibrosis in the KI mice. Metformin use was associated with significantly reduced fibrosis and lipid accumulation in WT mice. In contrast, in the KI mice, the drug was associated with worsened fibrosis.
conclusionsThese data indicate that reduced phosphorylation of ACC after renal injury contributes to the development of TIF, and that phosphorylation of ACC is required for metformin's antifibrotic action in the kidney.
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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.