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Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechani...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141311/ https://www.ncbi.nlm.nih.gov/pubmed/37122566 http://dx.doi.org/10.3389/fmolb.2023.1166333 |
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author | Su, Kuan-Jui Chen, Xing-Ying Gong, Rui Zhao, Qi Hu, Shi-Di Feng, Mei-Chen Li, Ye Lin, Xu Zhang, Yin-Hua Greenbaum, Jonathan Tian, Qing Shen, Hui Xiao, Hong-Mei Shen, Jie Deng, Hong-Wen |
author_facet | Su, Kuan-Jui Chen, Xing-Ying Gong, Rui Zhao, Qi Hu, Shi-Di Feng, Mei-Chen Li, Ye Lin, Xu Zhang, Yin-Hua Greenbaum, Jonathan Tian, Qing Shen, Hui Xiao, Hong-Mei Shen, Jie Deng, Hong-Wen |
author_sort | Su, Kuan-Jui |
collection | PubMed |
description | Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies. |
format | Online Article Text |
id | pubmed-10141311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101413112023-04-29 Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo Su, Kuan-Jui Chen, Xing-Ying Gong, Rui Zhao, Qi Hu, Shi-Di Feng, Mei-Chen Li, Ye Lin, Xu Zhang, Yin-Hua Greenbaum, Jonathan Tian, Qing Shen, Hui Xiao, Hong-Mei Shen, Jie Deng, Hong-Wen Front Mol Biosci Molecular Biosciences Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies. Frontiers Media S.A. 2023-04-14 /pmc/articles/PMC10141311/ /pubmed/37122566 http://dx.doi.org/10.3389/fmolb.2023.1166333 Text en Copyright © 2023 Su, Chen, Gong, Zhao, Hu, Feng, Li, Lin, Zhang, Greenbaum, Tian, Shen, Xiao, Shen and Deng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Su, Kuan-Jui Chen, Xing-Ying Gong, Rui Zhao, Qi Hu, Shi-Di Feng, Mei-Chen Li, Ye Lin, Xu Zhang, Yin-Hua Greenbaum, Jonathan Tian, Qing Shen, Hui Xiao, Hong-Mei Shen, Jie Deng, Hong-Wen Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo |
title | Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
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title_full | Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
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title_fullStr | Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
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title_full_unstemmed | Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
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title_short | Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo
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title_sort | systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141311/ https://www.ncbi.nlm.nih.gov/pubmed/37122566 http://dx.doi.org/10.3389/fmolb.2023.1166333 |
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