Journal article
Adiposity, metabolomic biomarkers and risk of nonalcoholic fatty liver disease: a case-cohort study
- Abstract:
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Background
Globally, the burden of obesity and associated nonalcoholic fatty liver disease (NAFLD) are rising, but little is known about the role that circulating metabolomic biomarkers play in mediating their association.
Objectives
We aimed to examine the observational and genetic associations of adiposity with metabolomic biomarkers and the observational associations of metabolomic biomarkers with incident NAFLD.
Methods
A case-subcohort study within the prospective China Kadoorie Biobank included 176 NAFLD cases and 180 subcohort individuals and measured 1208 metabolites in stored baseline plasma using a Metabolon assay. In the subcohort the observational and genetic associations of BMI with biomarkers were assessed using linear regression, with adjustment for multiple testing. Cox regression was used to estimate adjusted HRs for NAFLD associated with biomarkers.
Results
In observational analyses, BMI (kg/m2; mean: 23.9 in the subcohort) was associated with 199 metabolites at a 5% false discovery rate. The effects of genetically elevated BMI with specific metabolites were directionally consistent with the observational associations. Overall, 35 metabolites were associated with NAFLD risk, of which 15 were also associated with BMI, including glutamate (HR per 1-SD higher metabolite: 1.95; 95% CI: 1.48, 2.56), cysteine-glutathione disulfide (0.44; 0.31, 0.62), diaclyglycerol (C32:1) (1.71; 1.24, 2.35), behenoyl dihydrosphingomyelin (C40:0) (1.92; 1.42, 2.59), butyrylcarnitine (C4) (1.91; 1.38, 2.35), 2-hydroxybehenate (1.81; 1.34, 2.45), and 4-cholesten-3-one (1.79; 1.27, 2.54). The discriminatory performance of known risk factors was increased when 28 metabolites were also considered simultaneously in the model (weighted C-statistic: 0.84 to 0.90; P < 0.001).
Conclusions
Among relatively lean Chinese adults, a range of metabolomic biomarkers are associated with NAFLD risk and these biomarkers may lie on the pathway between adiposity and NAFLD.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 3.8MB, Terms of use)
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- Publisher copy:
- 10.1093/ajcn/nqab392
Authors
- Publisher:
- Oxford University Press
- Journal:
- The American Journal of Clinical Nutrition More from this journal
- Volume:
- 115
- Issue:
- 3
- Pages:
- 799–810
- Publication date:
- 2021-12-13
- Acceptance date:
- 2021-11-18
- DOI:
- EISSN:
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1938-3207
- ISSN:
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0002-9165
- Pmid:
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34902008
- Language:
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English
- Keywords:
- Pubs id:
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1224493
- Local pid:
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pubs:1224493
- Deposit date:
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2022-02-09
Terms of use
- Copyright holder:
- Pang et al.
- Copyright date:
- 2021
- Rights statement:
- ©2021 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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