{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:33:35Z","timestamp":1793943215732,"version":"4.8.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) grant funded by the Korean government (Ministry of Science and ICT)","doi-asserted-by":"publisher","award":["NRF-2019R1F1A1057588"],"award-info":[{"award-number":["NRF-2019R1F1A1057588"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Several adult omics studies have been conducted to understand the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, the histological features of children are different from those of adults, and the onset and progression of pediatric NAFLD are not fully understood. In this study, we aimed to evaluate the metabolome profile and metabolic pathway changes associated with pediatric NAFLD to elucidate its pathophysiology and to develop machine learning-based NAFLD diagnostic models. We analyzed the metabolic profiles of healthy control, lean NAFLD, overweight control, and overweight NAFLD groups of children and adolescent participants (N = 165) by assessing plasma samples. Additionally, we constructed diagnostic models by applying three machine learning methods (ElasticNet, random forest, and XGBoost) and multiple logistic regression by using NAFLD-specific metabolic features, genetic variants, and clinical data. We identified 18 NAFLD-specific metabolic features and metabolic changes in lipid, glutathione-related amino acid, and branched-chain amino acid metabolism by comparing the control and NAFLD groups in the overweight pediatric population. Additionally, we successfully developed and cross-validated diagnostic models that showed excellent diagnostic performance (ElasticNet and random forest model: area under the receiver operating characteristic curve, 0.95). Metabolome changes in the plasma of pediatric patients with NAFLD are associated with the pathophysiology of the disease and can be utilized as a less-invasive approach to diagnosing the disease.<\/jats:p>","DOI":"10.3390\/metabo12090881","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T04:49:22Z","timestamp":1663562962000},"page":"881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Association of Metabolic Signatures with Nonalcoholic Fatty Liver Disease in Pediatric Population"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-1504","authenticated-orcid":false,"given":"Woori","family":"Chae","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea"},{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hallym University Sacred Heart Hospital, Anyang 14068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-9954","authenticated-orcid":false,"given":"Ki Young","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9760-297X","authenticated-orcid":false,"given":"Jin Soo","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Sung","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-8273","authenticated-orcid":false,"given":"Joo-Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea"},{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. 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