Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis
Abstract The mechanisms underlying metabolically healthy obesity (MHO) in pediatrics remain poorly understood. This study aims to evaluate the plasma metabolome of MHO versus metabolically unhealthy obesity (MUO) in Asian children and adolescents, to identify key metabolic drivers that undergird the...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-09132-6 |
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| author | Daniel Zhi Wei Ng Yu Hao Shie Sandheep Ransilu Piyasanka Dorinda Yan Qin Kioh Andrew Anjian Sng Bee Wah Lee Yung Seng Lee Eric Chun Yong Chan Delicia Shu Qin Ooi |
| author_facet | Daniel Zhi Wei Ng Yu Hao Shie Sandheep Ransilu Piyasanka Dorinda Yan Qin Kioh Andrew Anjian Sng Bee Wah Lee Yung Seng Lee Eric Chun Yong Chan Delicia Shu Qin Ooi |
| author_sort | Daniel Zhi Wei Ng |
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| description | Abstract The mechanisms underlying metabolically healthy obesity (MHO) in pediatrics remain poorly understood. This study aims to evaluate the plasma metabolome of MHO versus metabolically unhealthy obesity (MUO) in Asian children and adolescents, to identify key metabolic drivers that undergird the MUO phenotype. MHO and MUO were defined by the absence or presence of metabolic syndrome criteria, respectively. We conducted untargeted metabolomics analysis on plasma samples from children and adolescents without obesity (n = 24), with MHO (n = 65) and with MUO (n = 222). Multivariate data analyses identified key metabolites differentiating the groups. Logistic regression assessed metabolite associations with metabolic conditions, while Spearman’s correlation evaluated their links to cardiometabolic parameters. Metabolites such as plasma fatty acids, amino acids and 1,5-anhydroglucitol differentiated MHO from MUO, correlating significantly with parameters of glucose homeostasis. Plasma branched-chain amino acids and 3-hydroxyisobutyric acid were elevated while 1,5-anhydroglucitol was reduced in pediatrics with obesity and abnormal glucose tolerance compared to those with obesity and normal glucose tolerance. Our study revealed distinct metabolome alterations between MHO and MUO in Asian children and adolescents. Notably, we identified that these metabolomic differences between MHO and MUO are primarily linked to abnormal glucose homeostasis, highlighting potential metabolic targets for improving health outcomes in pediatric obesity. |
| format | Article |
| id | doaj-art-02676cf21c214b289c8fb9d1a4a6e75f |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-02676cf21c214b289c8fb9d1a4a6e75f2025-08-20T03:03:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-09132-6Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasisDaniel Zhi Wei Ng0Yu Hao Shie1Sandheep Ransilu Piyasanka2Dorinda Yan Qin Kioh3Andrew Anjian Sng4Bee Wah Lee5Yung Seng Lee6Eric Chun Yong Chan7Delicia Shu Qin Ooi8Department of Pharmacy and Pharmaceutical Science, Faculty of Science, National University of SingaporeDepartment of Pharmacy and Pharmaceutical Science, Faculty of Science, National University of SingaporeDepartment of Pharmacy and Pharmaceutical Science, Faculty of Science, National University of SingaporeDepartment of Pharmacy and Pharmaceutical Science, Faculty of Science, National University of SingaporeDepartment of Paediatrics, National University of Singapore, Yong Loo Lin School of MedicineDepartment of Paediatrics, National University of Singapore, Yong Loo Lin School of MedicineDepartment of Paediatrics, National University of Singapore, Yong Loo Lin School of MedicineDepartment of Pharmacy and Pharmaceutical Science, Faculty of Science, National University of SingaporeDepartment of Paediatrics, National University of Singapore, Yong Loo Lin School of MedicineAbstract The mechanisms underlying metabolically healthy obesity (MHO) in pediatrics remain poorly understood. This study aims to evaluate the plasma metabolome of MHO versus metabolically unhealthy obesity (MUO) in Asian children and adolescents, to identify key metabolic drivers that undergird the MUO phenotype. MHO and MUO were defined by the absence or presence of metabolic syndrome criteria, respectively. We conducted untargeted metabolomics analysis on plasma samples from children and adolescents without obesity (n = 24), with MHO (n = 65) and with MUO (n = 222). Multivariate data analyses identified key metabolites differentiating the groups. Logistic regression assessed metabolite associations with metabolic conditions, while Spearman’s correlation evaluated their links to cardiometabolic parameters. Metabolites such as plasma fatty acids, amino acids and 1,5-anhydroglucitol differentiated MHO from MUO, correlating significantly with parameters of glucose homeostasis. Plasma branched-chain amino acids and 3-hydroxyisobutyric acid were elevated while 1,5-anhydroglucitol was reduced in pediatrics with obesity and abnormal glucose tolerance compared to those with obesity and normal glucose tolerance. Our study revealed distinct metabolome alterations between MHO and MUO in Asian children and adolescents. Notably, we identified that these metabolomic differences between MHO and MUO are primarily linked to abnormal glucose homeostasis, highlighting potential metabolic targets for improving health outcomes in pediatric obesity.https://doi.org/10.1038/s41598-025-09132-6Abnormal glucose toleranceChildren and adolescents with obesityMetabolically healthy obesityMetabolically unhealthy obesityMetabolic syndromePlasma metabolomics |
| spellingShingle | Daniel Zhi Wei Ng Yu Hao Shie Sandheep Ransilu Piyasanka Dorinda Yan Qin Kioh Andrew Anjian Sng Bee Wah Lee Yung Seng Lee Eric Chun Yong Chan Delicia Shu Qin Ooi Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis Scientific Reports Abnormal glucose tolerance Children and adolescents with obesity Metabolically healthy obesity Metabolically unhealthy obesity Metabolic syndrome Plasma metabolomics |
| title | Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis |
| title_full | Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis |
| title_fullStr | Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis |
| title_full_unstemmed | Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis |
| title_short | Metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis |
| title_sort | metabolome alterations in pediatric metabolically unhealthy obesity are primarily linked to abnormal glucose homeostasis |
| topic | Abnormal glucose tolerance Children and adolescents with obesity Metabolically healthy obesity Metabolically unhealthy obesity Metabolic syndrome Plasma metabolomics |
| url | https://doi.org/10.1038/s41598-025-09132-6 |
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