| Title: | Association between Accelerometer-derived Physical Activity-related Metabolic Signature and Stroke: A Cohort Study from UK Biobank |
| Journal: | The journal of nutrition health & aging |
| Published: | 8 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41207133/ |
| DOI: | https://doi.org/10.1016/j.jnha.2025.100715 |
Publication 18984
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Abstract
BACKGROUND: Accelerometer-derived physical activity is associated with reduced stroke risk. The biological pathways underpinning this relationship, however, are not yet understood. Herein, we aim to identify metabolic signatures associated with accelerometer-measured PA and investigate their relationships with reduced stroke incidence.</p>
METHOD: Utilizing UK Biobank accelerometer data, we derived physical activity into total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) and linked them to 249 NMR-quantified plasma metabolites. The metabolomic signatures (TPA-/MVPA-/LPA-metabolomic signatures) were developed through internal validation followed by elastic-net regression modeling. Cox proportional hazards models evaluated activity-stroke associations (adjusted for sociodemographic/genetic factors), followed by mediation analysis to quantify metabolomic signature effects.</p>
RESULTS: Through UK Biobank study (N = 29445; 14.1-year follow-up with 513 stroke events), we identified 195 TPA, 173 MVPA, and 164 LPA metabolite associations (FDR < 0.05), with 107, 92, and 15 validated, respectively. Elastic net-derived physical activity-metabolomic signatures (TPA-/MVPA-metabolomic signatures) correlated with physical activity intensities (r = 0.20-0.30, P < 0.001) and were associated with reduced stroke risk: TPA-metabolomic signatures (HR = 0.61, 95% CI: 0.44-0.87); MVPA-metabolomic signatures (HR = 0.50, 95%CI: 0.29-0.88). Mediation analyses showed TPA-metabolomic signatures and MVPA-metabolomic signatures explained 12.2% and 8.5% of physical activity-stroke associations (P < 0.001), implicating specific lipoprotein subclasses and lipids as key mediators.</p>
CONCLUSION: TPA-metabolomic signatures and MVPA-metabolomic signatures, particularly the 11 key metabolites included, significantly mediate the association between accelerometer-derived physical activity and stroke risk.</p>
17 Keywords
- Accelerometry
- Aged
- Biological Specimen Banks
- Cohort Studies
- Exercise
- Female
- Humans
- Incidence
- Male
- Metabolome
- Metabolomics
- Middle Aged
- Proportional Hazards Models
- Risk Factors
- Stroke
- UK Biobank
- United Kingdom
12 Authors
- Bowen Tan
- Hewanmeng Geng
- Zeyu Hao
- Zhirong Li
- Chengxiang Hu
- Tian Yu
- Pengyu Wang
- Yuanhao Chen
- Zhongping Feng
- Lina Jin
- Baofeng Xu
- Rui Liu
2 Applications
| Application ID | Title |
|---|---|
| 625593 | Risk Factor Analysis and Disease Prediction for Brain Health Disorders and Metabolic-Cardiovascular Diseases |
| 710075 | Risk Factors and Disease Prediction for Cognitive Function, Brain Structure, Cardiovascular and Neurodegenerative Diseases, and Metabolic Disorders |
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