{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T15:22:08Z","timestamp":1767972128493,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["31L0057"],"award-info":[{"award-number":["31L0057"]}]},{"name":"German Federal Ministry of Education and Research","award":["031L0058"],"award-info":[{"award-number":["031L0058"]}]},{"name":"German Federal Ministry of Education and Research","award":["031L0258H"],"award-info":[{"award-number":["031L0258H"]}]},{"name":"Max Planck Society","award":["31L0057"],"award-info":[{"award-number":["31L0057"]}]},{"name":"Max Planck Society","award":["031L0058"],"award-info":[{"award-number":["031L0058"]}]},{"name":"Max Planck Society","award":["031L0258H"],"award-info":[{"award-number":["031L0258H"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and is associated with overweight and insulin resistance (IR). Almost nothing is known about in vivo alterations of liver metabolism in NAFLD, especially in the early stages of non-alcoholic steatohepatitis (NASH). Here, we used a complex mathematical model of liver metabolism to quantify the central hepatic metabolic functions of 71 children with biopsy-proven NAFLD. For each patient, a personalized model variant was generated based on enzyme abundances determined by mass spectroscopy. Our analysis revealed statistically significant alterations in the hepatic carbohydrate, lipid, and ammonia metabolism, which increased with the degree of obesity and severity of NAFLD. Histologic features of NASH and IR displayed opposing associations with changes in carbohydrate and lipid metabolism but synergistically decreased urea synthesis in favor of the increased release of glutamine, a driver of liver fibrosis. Taken together, our study reveals already significant alterations in the NASH liver of pediatric patients, which, however, are differently modulated by the simultaneous presence of IR.<\/jats:p>","DOI":"10.3390\/ijms231911072","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T01:47:06Z","timestamp":1663811226000},"page":"11072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alterations of Central Liver Metabolism of Pediatric Patients with Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-9940","authenticated-orcid":false,"given":"Nikolaus","family":"Berndt","sequence":"first","affiliation":[{"name":"Institute of Computer-Assisted Cardiovascular Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3642-0838","authenticated-orcid":false,"given":"Christian A.","family":"Hudert","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Eckstein","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Loddenkemper","sequence":"additional","affiliation":[{"name":"Gemeinschaftspraxis fuer Pathologie Pathotres, 12247 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Henning","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Bufler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Meierhofer","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Facility, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingolf","family":"Sack","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Wiegand","sequence":"additional","affiliation":[{"name":"Center for Chronically Sick Children, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-6475","authenticated-orcid":false,"given":"Iwona","family":"Wallach","sequence":"additional","affiliation":[{"name":"Institute of Computer-Assisted Cardiovascular Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann-Georg","family":"Holzh\u00fctter","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/ijo.2010.106","article-title":"Obese boys at increased risk for nonalcoholic liver disease: Evaluation of 16,390 overweight or obese children and adolescents","volume":"34","author":"Wiegand","year":"2010","journal-title":"Int. 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Cells, 8.","DOI":"10.3390\/cells8050512"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:36:24Z","timestamp":1760142984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":46,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911072"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911072","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]}}}