Liver Metabolomic Profiling Reveals Distinct Signatures Between Steatosis and Metabolic Dysfunction‐Associated Steatohepatitis - UTU Research Portal

A1 Refereed original research article in a scientific journal

Liver Metabolomic Profiling Reveals Distinct Signatures Between Steatosis and Metabolic Dysfunction‐Associated Steatohepatitis

Authors: Palomurto, Saana; Flam, Emily; Kaminska, Dorota; Virtanen, Kirsi A.; Kärjä, Vesa; Käkelä, Pirjo; Pajukanta, Päivi; Eberlé, Delphine; Haas, Joel T.; Raverdy, Violeta; Caiazzo, Robert; Pattou, François; Staels, Bart; Pihlajamäki, Jussi; Männistö, Ville

Publisher: Wiley-Blackwell

Publication year: 2026

Journal: Liver International

Article number: e70552

Volume: 46

Issue: 3

ISSN: 1478-3223

eISSN: 1478-3231

DOI: https://doi.org/10.1111/liv.70552

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Partially Open Access publication channel

Web address : https://doi.org/10.1111/liv.70552

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/515654524

Self-archived copy's licence: CC BY NC ND

Self-archived copy's version: Publisher`s PDF

Abstract

Background and Aims

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disease worldwide, is closely linked to obesity and metabolic syndrome. The reason some patients with MASLD develop metabolic dysfunction-associated steatohepatitis (MASH) and which metabolic changes in the liver are linked to its progression are unclear.

Methods

A non-targeted metabolomics analysis was performed on liver samples from 106 Finnish patients with severe obesity (71 females, mean age ± SD: 48.6 ± 8.7 years, body mass index: 41.6 ± 5.2 kg/m²) selected for laparoscopic gastric bypass surgery. Liver metabolomics and liver RNA sequencing data were used to study metabolic differences between those with steatosis and those with MASH. Validation was performed in a French cohort of 227 patients with obesity and MASLD.

Results

Overall, 45 metabolites differed between patients with steatosis and those with MASH. Novel MASH-associated metabolites included n-acetylneuraminate (β = 0.276), pentose acid (β = −0.290), UDP-galactose (β = −0.413), gamma/beta-tocopherol (β = −0.317), and guanidinosuccinate (β = −0.289) (all p < 0.05). In the validation cohort, 8 of 20 metabolites, including n-acetylneuraminate and plasmalogens 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE(P-16:0/20:4) and 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE(P-18:0/20:4), were linked to MASH (p < 0.05). The 45 significantly altered metabolites formed two clusters with different associations with metabolic parameters, depending on their correlation with liver histological features. Kyoto Encyclopedia of Genes and Genomes analysis revealed that elevated metabolites in MASH were associated with inflammatory pathways; those decreased in MASH were linked to fatty acid degradation and amino acid and pyruvate metabolism.

Conclusion

Transitioning from simple steatosis to MASH is associated with distinct alterations in liver metabolites and systemic metabolic traits, highlighting disease progression-associated pathways.

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Liver International - 2026 - Palomurto - Liver Metabolomic Profiling Reveals Distinct Signatures Between Steatosis and.pdf

Funding information in the publication:
S.P. was supported by the Finnish Medical Foundation, Mary and Georg C. Ehrnrooth Foundation, Kuopio University Hospital Research Foundation, and State Research Funding for university-level health research. The Kuopio Obesity Surgery Study was supported by the Finnish Diabetes Research Foundation, Kuopio University Hospital Project grants (EVO/VTR grants 2005–2021), Academy of Finland grant (Contract no. 138006), Finnish Cultural Foundation, and University of Eastern Finland Spearhead Funding (J.P.). V.M. was supported by the Finnish Medical Foundation, Sigrid Jusélius Foundation, and State Research Funding for University-level health research, Kuopio University Hospital, Wellbeing Service County of North Savo. This work was also supported by the Government of France Future Investments Program (PRECINASH, ANR-16-RHUS-0006; European Genomic Institute for Diabetes, ANR-10-LABX-0046). J.T.H. received an European Research Council Starting Grant (Metabo3DC contract number: 101042759). The researchers are independent of the funders. The funding sources had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; the preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication.