ArticleCell metabolism2020
Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly.
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Article in Cell metabolism, 2020. 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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86citing papers in PubMed, 1 pooled it
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- The causal relationship between 179 lipid species and urolithiasis: a bidirectional and multivariable Mendelian randomization study combined with meta-analysis.Lipids in health and disease · 2025Pooled it
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- Cell therapy comparison of dental pulp stem cells, hepatocytes, and their exosomes for liver fibrosis treatment in rats.Animal models and experimental medicine · 2026Article
- Inhibition of the SerpinB3/protease-activated receptor 2 axis reduces liver cancer development and affects lipid metabolism.British journal of cancer · 2026Article
- Metabolic dysfunction-associated steatohepatitis exacerbated by Clostridium perfringens-derived ammonia is attenuated by tripeptide DT-109.The Journal of clinical investigation · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Response to Kawamoto et al.EMBO reports · 2026Article
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- P5CS-coupled proline metabolism manipulates metabolic dysfunction-associated steatotic liver disease.Life metabolism · 2026Article
- Unraveling the Mechanisms of Wuling Powder Against MASLD by Integrated Metabolomics-Gut Microbiota-Serum Pharmacochemistry.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Exploring key genes in NAFLD linked to glutamine metabolism: A comprehensive analysis combining multi-omics, machine learning and SHAP.Asia Pacific journal of clinical nutrition · 2026Article
- Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on "Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome".Clinical and molecular hepatology · 2026Article
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Metabolic dysfunction-associated steatotic liver disease alters brain function and behavior: Insights from liver-targeted siRNA therapy.Science advances · 2025Article
- Targeting hepatocyte-specific SLC2A8 blocks hepatic steatosis and dissociates TCA cycle flux inhibition from glutamine anaplerosis.Hepatology communications · 2025Article
- Linc01271 promotes lipid synthesis and MASLD/MASH progression via miR-149-3p/RAB35 axis.Cellular and molecular life sciences : CMLS · 2025Article
- Hesperetin Protects from Palmitic-Acid-Induced Lipotoxicity through the Inhibition of Glutaminolysis, mTORC1 Signaling, and Limited Apoptosis.Journal of agricultural and food chemistry · 2025Article
- Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV.International journal of molecular sciences · 2025Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 10 institutions in 3 countries.
Jorge SimonLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Maitane Nuñez-GarcíaDepartment of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain.
Pablo Fernández-TussyLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Lucía Barbier-TorresLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
David Fernández-RamosLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Beatriz Gómez-SantosDepartment of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain.
Xabier BuquéDepartment of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain; Biocruces Health Research Institute, 48903 Barakaldo, Bizkaia, Spain.
Fernando Lopitz-OtsoaLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Naroa Goikoetxea-UsandizagaLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Marina Serrano-MaciaLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Rubén Rodriguez-AgudoLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Maider BizkarguenagaLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Imanol Zubiete-FrancoLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Virginia Gutiérrez-de JuanLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Diana CabreraMetabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Cristina AlonsoOwl Metabolomics, 48610 Derio, Bizkaia, Spain.
Paula IruzubietaGastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain; Clinical and Traslational Digestive Research Group, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain.
Manuel Romero-GomezUnit for the Clinical Management of Digestive Diseases, Hospital Universitario Virgen del Rocío, CIBERehd, University of Seville, 41013 Seville, Spain.
Sebastiaan van LiempdMetabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Azucena CastroOwl Metabolomics, 48610 Derio, Bizkaia, Spain.
Ruben NogueirasDepartment of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela-Instituto de Investigación Sanitaria, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Galician Agency of Innovation (GAIN), Xunta de Galicia, 15782 Santiago de Compostela, Spain.
Marta Varela-ReyLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Juan Manuel Falcón-PérezMetabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain; Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Bizkaia, Spain.
Erica VillaDepartment of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, 41121 Modena, Italy.
Javier CrespoGastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain; Clinical and Traslational Digestive Research Group, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain.
Shelly C LuDivision of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States.
Jose M MatoLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain.
Patricia AspichuetaDepartment of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain; Biocruces Health Research Institute, 48903 Barakaldo, Bizkaia, Spain.
Teresa C DelgadoLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain. Electronic address: tcardoso@cicbiogune.es.
María Luz Martínez-ChantarLiver Disease Laboratory, Liver Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain. Electronic address: mlmartinez@cicbiogune.es.
CIC bioGUNE · ESCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESUniversity of the Basque Country · ESInstituto de Investigación Marqués de Valdecilla · ESOWL (Spain) · ESCedars-Sinai Medical Center · USCenter for Research in Molecular Medicine and Chronic Diseases · ESHospital Universitario Virgen del Rocío · ESIkerbasque · ESUniversity of Modena and Reggio Emilia · IT
Funding
Role of SAMe in Pathogenesis and Treatment of Non-Alcholic Fatty Liver DiseaseR01AT001576 · NCCIH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LU, SHELLY CHI-LOO · 2002 to 2018
$5.0MNCCIH NIH HHS R01 AT001576
Abstract
Non-alcoholic steatohepatitis (NASH) is characterized by the accumulation of hepatic fat in an inflammatory/fibrotic background. Herein, we show that the hepatic high-activity glutaminase 1 isoform (GLS1) is overexpressed in NASH. Importantly, GLS1 inhibition reduces lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. We suggest that under these circumstances, defective glutamine fueling of anaplerotic mitochondrial metabolism and concomitant reduction of oxidative stress promotes a reprogramming of serine metabolism, wherein serine is shifted from the generation of the antioxidant glutathione and channeled to provide one-carbon units to regenerate the methionine cycle. The restored methionine cycle can induce phosphatidylcholine synthesis from the phosphatidylethanolamine N-methyltransferase-mediated and CDP-choline pathways as well as by base-exchange reactions between phospholipids, thereby restoring hepatic phosphatidylcholine content and very-low-density lipoprotein export. Overall, we provide evidence that hepatic GLS1 targeting is a valuable therapeutic approach in NASH.
Indexed as
AdultAnimalsCholineDisease Models, AnimalFemaleGlutaminaseHepatocytesHumansLipid MetabolismLipoproteins, VLDLLiverMaleMethionineMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseOxidative StressCholineGlutaminaseLipoproteins, VLDLMethioninePhospholipidsTriglyceridesvery low density lipoprotein triglyceridefolate cycleGLS1GLS2glutaminasemethionine cycleNAFLDNASHphospholipidsTCA cycleVLDL
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