Evidence mapPaperPMID 42205264Full record

ArticleFrontiers in endocrinology2026

Metabolomic signatures mediate the association between physical frailty and metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

Doudou Li, Yacong Bo, Yao Chen, Zhitian Guo, Li Li, Wenjie Zhang, Mingyi Xue, Yongjian Zhu, Liuhang Ren, Tingting Li and 1 more

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Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Doudou Li *The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Yacong Bo *School of Public Health, Zhengzhou University, Zhengzhou, China.
Yao ChenThe Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhitian GuoSchool of Public Health, Zhengzhou University, Zhengzhou, China.
Li LiSchool of Public Health, Zhengzhou University, Zhengzhou, China.
Wenjie ZhangSchool of Public Health, Zhengzhou University, Zhengzhou, China.
Mingyi XueNational Health Commission (NHC) Key Laboratory of Birth Defects Prevention & Institute of Reproductive Health, Henan Academy of Innovations in Medical Science, Zhengzhou, China.
Yongjian ZhuDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Liuhang RenThe Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Tingting LiThe Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhan GaoThe Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Physical frailty is linked to metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying metabolic mechanisms remain unclear. This study aimed to identify a frailty-related metabolic signature and examine its association with incident MASLD and its mediating role in the frailty-MASLD relationship. Methods: We analysed data from 244,187 UK Biobank participants. Frailty was assessed using the Fried Frailty Phenotype. Incident MASLD was ascertained via hospital records and death registries. An elastic net regression model identified frailty-associated metabolites to construct a weighted metabolic signature. Cox proportional hazards models estimated associations with MASLD risk, and mediation analysis quantified the signature's contribution. Results: Over a median follow-up of 13.7 years, 3,408 incident MASLD cases occurred. A 96-metabolite signature was identified. Each 1-standard deviation increase in the signature was associated with a 21% higher MASLD risk (HR = 1.21, 95% CI: 1.16-1.25). Compared with robust participants, pre-frail and frail individuals had HRs of 1.51 (95% CI: 1.40-1.63) and 2.22 (95% CI: 1.97-2.50), respectively. The metabolic signature mediated 4.25% of the frailty-MASLD association. Conclusion: Frailty and its associated metabolic signature are independently associated with increased incident MASLD risk. The signature partially mediates this relationship, suggesting metabolic dysregulation links physical frailty to hepatic steatosis. Identifying this signature may enable earlier MASLD detection in frail individuals.

Indexed as

Fatty LiverFrailtyMetabolic DiseasesMetabolomeNon-alcoholic Fatty Liver DiseaseAgedFemaleFollow-Up StudiesHumansMaleMetabolomicsMiddle AgedProspective StudiesRisk FactorsUnited Kingdommediationmetabolic dysfunction-associated steatotic liver diseasemetabolic signaturephysical frailtyUK Biobank

Identifiers

PMID42205264
PMCPMC13201151

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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 Socratic graph.