{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:08:00Z","timestamp":1777954080216,"version":"3.51.4"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2021YFA1301102"],"award-info":[{"award-number":["2021YFA1301102"]}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["ZCLQ24H0601"],"award-info":[{"award-number":["ZCLQ24H0601"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Zhejiang Key Laboratory of Intelligent Rehabilitation and Translational Neuroelectronics","award":["2024E10108"],"award-info":[{"award-number":["2024E10108"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The detrimental cycle of sarcopenic obesity (SO) significantly reduces quality of life in older adults, while the mechanisms are still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We first analyzed the incidence of SO using the CHARLS database. We identified key genes by integrating differentially expressed genes, weighted gene co-expression network analysis, and targets of gut microbiota metabolites, refining the selection through machine learning methods (LASSO, XGBoost, SVM-REF, Random Forest). These genes were validated through single-cell sequencing, receiver operating characteristic analysis, and Muscle immunohistochemistry in a high-fat-diet (HFD) induced mouse model. Further analyses comprised immune infiltration profiling, pathway enrichment, and transcriptional regulation analysis. Additionally, we explored the relationships between key genes and autophagy, ferroptosis, and immunity responses. Finally, we predicted and evaluated potential therapeutic compounds via the CMap database and molecular docking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SO incidence in China increased significantly from 16.1% (2011) to 20.4% (2018). Machine learning identified ALDH1A3, CSF1R, and PHGDH as key genes. These genes were validated in external muscle single-cell datasets, demonstrating robust diagnostic performance with AUC values exceeding 0.72 across four independent GEO cohorts. Following an HFD intervention in mice, ALDH1A3 and CSF1R expression in muscle tissue was significantly upregulated, while PHGDH showed a consistent upward trend that did not reach statistical significance. Immune infiltration analysis revealed a significant increase in resting NK cells in both obesity and sarcopenia states. Functional enrichment analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes linked the genes to transcriptional regulation pathways. The Cisbp_M4923 motif was identified as the most relevant transcription factor binding site. Finally, molecular docking simulations indicated stable binding of the top candidate compound, Birinapant, to the key gene targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ALDH1A3, CSF1R, and PHGDH serve as potential co-morbid biomarkers for SO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pcbi.1014225","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:25:20Z","timestamp":1777915520000},"page":"e1014225","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Co-morbid biomarkers for sarcopenic obesity associated with gut microbiota metabolites: From burden to treatment"],"prefix":"10.1371","volume":"22","author":[{"given":"Juehan","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haijun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianfang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2596-4918","authenticated-orcid":true,"given":"Zuobing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"pcbi.1014225.ref001","article-title":"Update on the obesity epidemic: Is the sharp rise of the evil empire truly levelling off?","author":"C Koliaki","year":"2023","journal-title":"Current Obesity Reports"},{"key":"pcbi.1014225.ref002","article-title":"A new framework for the diagnosis, staging and management of obesity in adults","author":"L Busetto","year":"2024","journal-title":"Nat Med"},{"key":"pcbi.1014225.ref003","doi-asserted-by":"crossref","first-page":"1197150","DOI":"10.3389\/fpubh.2024.1197150","article-title":"The role of education attainment on 24-hour movement behavior in emerging adults: evidence from a population-based study","volume":"12","author":"Y You","year":"2024","journal-title":"Front Public Health"},{"issue":"1","key":"pcbi.1014225.ref004","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: revised European consensus on definition and diagnosis","volume":"48","author":"AJ Cruz-Jentoft","year":"2019","journal-title":"Age Ageing"},{"issue":"21","key":"pcbi.1014225.ref005","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1002\/cam4.3428","article-title":"Sarcopenia and adverse health-related outcomes: An umbrella review of meta-analyses of observational studies","volume":"9","author":"L Xia","year":"2020","journal-title":"Cancer Med"},{"key":"pcbi.1014225.ref006","doi-asserted-by":"crossref","first-page":"155533","DOI":"10.1016\/j.metabol.2023.155533","article-title":"Epidemiology of sarcopenia: prevalence, risk factors, and consequences","volume":"144","author":"S Yuan","year":"2023","journal-title":"Metabolism-Clinical and Experimental"},{"issue":"5","key":"pcbi.1014225.ref007","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.clnu.2023.02.018","article-title":"Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) - 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