ArticleScientific reports2023
A gut microbial metabolite of linoleic acid ameliorates liver fibrosis by inhibiting TGF-β signaling in hepatic stellate cells.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Gut‑liver‑kidney axis: A systems biology framework for understanding and treating chronic kidney disease (Review).International journal of molecular medicine · 2026Review
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Conjugated Linoleic Acid Alleviates Hepatic Steatosis and Liver Damage in Estradiol-Induced FLHS Roosters by Reshaping Lipid Metabolism and Inhibiting the MAPK/NF-κB-Mediated Inflammation Cascade.Animals : an open access journal from MDPI · 2026Article
- Plasma metabolic signatures of healthy dietary patterns and risk of metabolic dysfunction-associated steatotic liver disease and cirrhosis.Hepatology international · 2026Article
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- Evaluation of the Therapeutic Potential ofNutrients · 2026Article
- Microbial Monotherapy With Leuconostoc sp LB-P8 Improves Inflammation and Fibrosis in Mouse Primary Sclerosing Cholangitis by Inhibiting Transforming Growth Factor β1/SMAD Signaling.Cellular and molecular gastroenterology and hepatology · 2026Article
- Article
- Gut microbiota-derived metabolites and host interactions in fibrotic diseases: mechanisms, cross-organ signatures, and therapeutic opportunities.Frontiers in microbiology · 2026Review
- Fatty liver reexamined choline and mitochondrial toxin amelioration.World journal of biological chemistry · 2025Review
- The role of metaorganismal lipid metabolism in human health and disease.Immunometabolism (Cobham, Surrey) · 2025Article
- Static magnetic field exposure modulates gut microbiota and host metabolism to alleviate high-fat diet-induced metabolic dysfunction-associated fatty liver disease.Zoological research · 2025Article
- A Gut Microbial Metabolite HYA Ameliorates Adipocyte Hypertrophy by Activating AMP-Activated Protein Kinase.Nutrients · 2025Article
- Efficacy and mechanism of action of harmine derivative H-2-104 against Echinococcus granulosus infection in mice.BMC veterinary research · 2025Article
- The Many Facets of PPAR-γ Agonism in Obesity and Associated Comorbidities: Benefits, Risks, Challenges, and Future Directions.Current obesity reports · 2025Review
- An Integration of RNA Sequencing and Network Pharmacology Approaches Predicts the Molecular Mechanisms of the Huo-Xue-Shen Formula in the Treatment of Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Gut-X axis.iMeta · 2025Review
- Mechanisms of gut microbiota in host fat deposition: metabolites, signaling pathways, and translational applications.Frontiers in microbiology · 2025Review
- D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress.Frontiers in nutrition · 2025Article
- Integrative network pharmacology, metabolomics and gut flora studies reveal mechanisms of action ofFrontiers in microbiology · 2025Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antidiabetic drug pioglitazone ameliorates insulin resistance by activating the transcription factor PPARγ. In addition to its blood glucose-lowering action, pioglitazone exerts pleiotropic effects including amelioration of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). The mechanism by which pioglitazone achieves this latter effect has remained unclear, however. We here show that pioglitazone administration increases the amount of linoleic acid (LA) metabolites in adipose tissue of KK-Ay mice. These metabolites are produced by lactic acid bacteria in the gut, and pioglitazone also increased the fraction of Lactobacillus in the gut microbiota. Administration of the LA metabolite HYA (10-hydroxy-cis-12-octadecenoic acid) to C57BL/6 J mice fed a high-fat diet improved liver histology including steatosis, inflammatory cell infiltration, and fibrosis. Gene ontology analysis of RNA-sequencing data for the liver revealed that the top category for genes downregulated by HYA treatment was related to extracellular matrix, and the expression of individual genes related to fibrosis was confirmed to be attenuated by HYA treatment. Mechanistically, HYA suppressed TGF-β-induced Smad3 phosphorylation and fibrosis-related gene expression in human hepatic stellate cells (LX-2). Our results implicate LA metabolites in the mechanism by which pioglitazone ameliorates liver fibrosis, and they suggest that HYA is a potential therapeutic for NAFLD/NASH.
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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.