ArticleJCI insight2025
Circulating metabolite signatures indicate differential gut-liver crosstalk in lean and obese MASLD.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Review
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Uncovering the similarities of lipidome-wide markers of carotid artery plaque and metabolic dysfunction-associated fatty liver disease: the Young Finns study.Scientific reports · 2026Article
- Article
- Cross-organ multi-omics profiling of microbiome and metabolome along the gut-liver axis in MASH model mice induced by western diet and MC4R knockout.Gut pathogens · 2026Article
- Alternatives to animal models in gastroenterology and hepatology research.Frontiers in pharmacology · 2026Review
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Primary Human Tissue Models for Metabolic Dysfunction-Associated Liver Disease - toward Streamlining Drug Discovery with Patient-Derived Assays.Advanced biology · 2025Review
- Review
- Peroxisome Dysfunction and Steatotic Liver Disease.International journal of molecular sciences · 2025Review
- Triglyceride-glucose-waist circumference index: A powerful tool for metabolic dysfunction-associated steatotic liver disease.World journal of hepatology · 2025Review
- Gut microbial signatures associated with the Indian lean MASLD phenotype.Frontiers in nutrition · 2025Review
- Decoding the heterogeneity of liver-resident macrophages in chronic liver diseases: therapeutic responses to immunomodulatory strategies.Frontiers in pharmacology · 2025Review
- The global landscape of lean metabolic dysfunction-associated steatotic liver disease: insight from Asia and the West.Frontiers in gastroenterology (Lausanne, Switzerland) · 2025Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUNDAlterations in circulating metabolites have been described in obese metabolic dysfunction-associated steatotic liver disease (MASLD), but data on lean MASLD are lacking. We investigated serum metabolites, including microbial bile acids and short-chain fatty acids (SCFAs), and their association with lean and obese MASLD.METHODSSerum samples from 204 people of European descent were allocated to groups: lean healthy, lean MASLD, obese healthy, and obese MASLD (n = 47). Liquid chromatography-mass spectrometry-based metabolomics and linear model analysis were performed. MASLD prediction was assessed based on least absolute shrinkage and selection operator regression. Functional effects of altered molecules were verified in organotypic 3D primary human liver cultures.RESULTSLean MASLD was characterized by elevated isobutyrate, methionine sulfoxide, propionate, and phosphatidylcholines. Patients with obese MASLD had increased sarcosine and decreased lysine and asymmetric dimethylarginine. Using metabolites, sex, and BMI, MASLD versus healthy could be predicted with a median AUC of 86.5% and 85.6% in the lean and obese subgroups, respectively. Functional experiments in organotypic 3D primary human liver cultures showed propionate and isobutyrate induced lipid accumulation and altered expression of genes involved in lipid and glucose metabolism.CONCLUSIONLean MASLD is characterized by a distinct metabolite pattern related to amino acid metabolism, lipids, and SCFAs, while metabolic pathways of lipid accumulation are differentially activated by microbial metabolites. We highlight an important role of microbial metabolites in MASLD, with implications for predictive and mechanistic assessment of liver disease across weight categories.FUNDINGRobert Bosch Stiftung, Swedish Research Council (2021-02801, 2023-03015, 2024-03401), ERC Consolidator Grant 3DMASH (101170408), Ruth and Richard Julin Foundation for Gastroenterology (2021-00158), SciLifeLab and Wallenberg National Program for Data-Driven Life Science (WASPDDLS22:006), Novo Nordisk Foundation (NNF23OC0085944, NNF23OC0084420), PMU-FFF (E-18/28/148-FEL).
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