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Epidemiology and Population Health

Association between metabolic signatures of predicted VAT mass and risk of MASLD and other chronic liver diseases

International Journal of Obesity (2026)Cite this article

Subjects

Abstract

Background and aims

Visceral adipose tissue (VAT) plays a key role in metabolic dysfunction, and it is increasingly recognised as a contributor to metabolic dysfunction-associated steatotic liver disease (MASLD) and other chronic liver conditions. However, the systemic metabolic pathways linking VAT to liver disease remain unclear. This study aimed to identify metabolic signatures associated with VAT and examine their potential role as mediators in the relationship between VAT accumulation and the risks of MASLD, cirrhosis and hepatoma.

Methods

This prospective study included 269,018 UK Biobank participants without baseline liver disease. Predicted VAT mass was estimated using sex-specific models on the basis of anthropometric and bioimpedance measures. Incident liver outcomes were identified via ICD-coded hospital records. A VAT-related metabolic signature was derived from 251 circulating metabolites by using elastic net regression. Associations with liver disease risks were assessed using Cox models. Mediation analysis estimated the proportion of the VAT–MASLD association explained by the metabolic signature.

Results

Over a median follow-up of 14.3 years, 2658 MASLD, 671 cirrhosis and 444 hepatoma cases occurred. Each standard deviation increase in VAT was associated with increased risks of MASLD (HR: 1.70; 95% CI: 1.62–1.79), cirrhosis (HR: 1.27; 95% CI: 1.15–1.40) and hepatoma (HR: 1.15; 95% CI: 1.02–1.30). The VAT-related metabolic signature (156 metabolites, primarily lipoprotein subclasses and lipids) was independently associated with MASLD (HR: 1.89; 95% CI: 1.72–2.08) and mediated 40.0% of the VAT–MASLD association. No significant mediation was observed for cirrhosis or hepatoma.

Conclusions

VAT and its metabolic signature are strongly associated with MASLD risk, partly explaining its pathogenesis through systemic metabolic alterations.

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Fig. 1: Restricted cubic spline analysis on the dose–response association between predicted VAT mass and incident MASLD.
Fig. 2: Causal mediation analysis of predicted VAT mass-related metabolic signatures on the relationship between predicted VAT mass and MASLD.
Fig. 3: Association of metabolites constituting the metabolic signature with predicted VAT mass and MASLD.
Fig. 4: Causal mediation analysis of predicted VAT mass on MASLD via metabolites.

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Data availability

The data for this study were obtained from the UK Biobank under Application Number 55794. Researchers wishing to access these data can apply directly through the UK Biobank website (www.ukbiobank.ac.uk).

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Acknowledgements

The authors wish to express their gratitude to all the participants of the UK Biobank and all individuals involved in establishing the UK Biobank study.

Funding

This study was supported by the National Natural Science Foundation of China (82173607) and the Guangdong Basic and Applied Basic Research Foundation (2024A1515011969).

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Author notes

  1. These authors contributed equally: Shi-Ao Wang, Hao-Wen Chen.

Authors and Affiliations

  1. Department of Epidemiology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, Guangzhou, China

    Shi-Ao Wang, Hao-Wen Chen, Qi Zhong, Zheng-Yun Xu, Yan-Fei Wei, Chen-Yu Zhang, Qiu-Rong Li, Zhan-Hui Shao, Kuan Liu, Bi-Fei Cao & Xian-Bo Wu

  2. Dermatology Hospital, Southern Medical University, Guangzhou, China

    Hao-Wen Chen

  3. Southern Medical University Institute for Global Health, Guangzhou, China

    Hao-Wen Chen

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Contributions

SAW provided substantial contributions to the conception and design. SAW, HWC, QZ and ZYX contributed to data analysis and interpretation. SAW and HWC drafted the article. QZ, ZYX, YFW, CYZ, QRL, ZHS, KL and BFC contributed to visualisation. All authors critically revised the article and approved the final version to be published.

Corresponding author

Correspondence to Xian-Bo Wu.

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Wang, SA., Chen, HW., Zhong, Q. et al. Association between metabolic signatures of predicted VAT mass and risk of MASLD and other chronic liver diseases. Int J Obes (2026). https://doi.org/10.1038/s41366-026-02067-6

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