The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern linked to obesity. Methods This study employed a Mendelian randomization approach to explore the causal influence of BMI on metabolic biomarkers and the subsequent risk of NAFLD. We analyzed data from mul...

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Main Authors: Bo Wang, Yanjiang Yang, Zhaoqiang Yin, Wenwen Yang
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84165-x
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author Bo Wang
Yanjiang Yang
Zhaoqiang Yin
Wenwen Yang
author_facet Bo Wang
Yanjiang Yang
Zhaoqiang Yin
Wenwen Yang
author_sort Bo Wang
collection DOAJ
description Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern linked to obesity. Methods This study employed a Mendelian randomization approach to explore the causal influence of BMI on metabolic biomarkers and the subsequent risk of NAFLD. We analyzed data from multiple sources, including 249 metabolic traits, to establish direct and mediating relationships among BMI, metabolic factors, and NAFLD risk. Results Our findings revealed a significant positive correlation between BMI and NAFLD across various datasets. We identified 176 metabolites associated with BMI, of which 106 were also linked to NAFLD. Importantly, 86 metabolites were found to mediate the relationship between BMI and NAFLD risk. Specifically, elevated levels of branched-chain amino acids, triglycerides, and certain cholesterol esters were notably associated with increased NAFLD risk, whereas changes in free cholesterol and phospholipid levels also played critical roles. Conclusion This study highlights the complex interactions between BMI, metabolic biomarkers, and NAFLD risk. By elucidating these relationships, we highlight potential targets for interventions aimed at reducing NAFLD incidence in populations with elevated BMI, ultimately contributing to improved metabolic health.
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spelling doaj-art-1f82021d6efa47b5b7f64a2bf078b3a32025-08-20T03:40:45ZengNature PortfolioScientific Reports2045-23222025-03-0115114210.1038/s41598-024-84165-xThe causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease riskBo Wang0Yanjiang Yang1Zhaoqiang Yin2Wenwen Yang3Faculty of Biology, University of FreiburgDepartment of Rheumatology and Immunology, The People’s Hospital of Qiandongnan Autonomous PrefectureDepartment of Minimally Invasive and Biliary Surgery, The Second Hospital of Hebei Medical UniversityThe First Clinical Medical College, Lanzhou UniversityAbstract Background Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern linked to obesity. Methods This study employed a Mendelian randomization approach to explore the causal influence of BMI on metabolic biomarkers and the subsequent risk of NAFLD. We analyzed data from multiple sources, including 249 metabolic traits, to establish direct and mediating relationships among BMI, metabolic factors, and NAFLD risk. Results Our findings revealed a significant positive correlation between BMI and NAFLD across various datasets. We identified 176 metabolites associated with BMI, of which 106 were also linked to NAFLD. Importantly, 86 metabolites were found to mediate the relationship between BMI and NAFLD risk. Specifically, elevated levels of branched-chain amino acids, triglycerides, and certain cholesterol esters were notably associated with increased NAFLD risk, whereas changes in free cholesterol and phospholipid levels also played critical roles. Conclusion This study highlights the complex interactions between BMI, metabolic biomarkers, and NAFLD risk. By elucidating these relationships, we highlight potential targets for interventions aimed at reducing NAFLD incidence in populations with elevated BMI, ultimately contributing to improved metabolic health.https://doi.org/10.1038/s41598-024-84165-xBody mass indexNonalcoholic fatty liver diseaseMendelian randomizationMetabolic biomarkersTriglycerides
spellingShingle Bo Wang
Yanjiang Yang
Zhaoqiang Yin
Wenwen Yang
The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
Scientific Reports
Body mass index
Nonalcoholic fatty liver disease
Mendelian randomization
Metabolic biomarkers
Triglycerides
title The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
title_full The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
title_fullStr The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
title_full_unstemmed The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
title_short The causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
title_sort causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
topic Body mass index
Nonalcoholic fatty liver disease
Mendelian randomization
Metabolic biomarkers
Triglycerides
url https://doi.org/10.1038/s41598-024-84165-x
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