ArticleCellular and molecular gastroenterology and hepatology2020
Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Metabolomic and lipidomic plasma profiles according to metabolic dysfunction-associated steatotic liver diseases (MASLD) stages in the absence of type 2 diabetes (T2D).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Pirfenidone Sensitizes Hepatic Stellate Cells to Ferroptosis by Reprogramming Glutamine and Serine Metabolism for GSH Depletion.Antioxidants (Basel, Switzerland) · 2026Article
- 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
- The pathogenesis of liver fibrosis in Wilson's disease: hepatocyte injury and regulation mediated by copper metabolism dysregulation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- From metabolic antagonism to homeostatic restoration: rewiring hepatic stellate cell bioenergetics for liver fibrosis reversal.Frontiers in medicine · 2026Review
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- Global research trends in biliary atresia-related liver fibrosis: a bibliometric analysis (2000-2024).Frontiers in pediatrics · 2026Article
- Metabolic reprogramming in hepatic stellate cells: unveiling a novel therapeutic target for liver fibrosis.Frontiers in physiology · 2026Review
- Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026Review
- Targeting the Glutaminolysis Pathway in Glaucoma-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Hesperetin Protects from Palmitic-Acid-Induced Lipotoxicity through the Inhibition of Glutaminolysis, mTORC1 Signaling, and Limited Apoptosis.Journal of agricultural and food chemistry · 2025Article
- A potential age-independent MASLD-related liver fibrosis index based on metabolic profiling.Scientific reports · 2025Article
- Review
- Article
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
- The metabolic shift of glutaminase 2 to glutaminase 1 promotes LGR5 + progenitor cell proliferation in liver cirrhosis.Cellular and molecular life sciences : CMLS · 2025Article
- Disrupted minor intron splicing activates reductive carboxylation-mediated lipogenesis to drive metabolic dysfunction-associated steatotic liver disease progression.The Journal of clinical investigation · 2025Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsNonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSCs) and liver fibrogenesis in mice. However, it is unclear how changes in HSC glutamine metabolism contribute to net changes in hepatic glutaminolytic activity during fibrosis progression, or whether this could be used to track fibrogenic activity in NASH. We postulated that increased HSC glutaminolysis marks active scarring in NASH.
methodsGlutaminolysis was assessed in mouse NASH fibrosis models and in NASH patients. Serum and liver levels of glutamine and glutamate and hepatic expression of glutamine transporter/metabolic enzymes were correlated with each other and with fibrosis severity. Glutaminolysis was disrupted in HSCs to examine if this directly influenced fibrogenesis.
resultsThe serum glutamate/glutamine ratio increased and correlated with its hepatic ratio, myofibroblast content, and fibrosis severity. Healthy livers almost exclusively expressed liver-type glutaminase (Gls2); Gls2 protein localized in zone 1 hepatocytes, whereas glutamine synthase was restricted to zone 3 hepatocytes. In fibrotic livers, Gls2 levels reduced and glutamine synthase zonality was lost, but both Slc1a5 (glutamine transporter) and kidney-type Gls1 were up-regulated; Gls1 protein was restricted to stromal cells and accumulated in fibrotic septa. Hepatocytes did not compensate for decreased Gls2 by inducing Gls1. Limiting glutamine or directly inhibiting GLS1 inhibited growth and fibrogenic activity in cultured human HSCs. Compared with healthy livers, fibrotic livers were
conclusionsGlutaminolysis is a potential diagnostic marker and therapeutic target during NASH fibrosis progression.
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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.