{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:40:48Z","timestamp":1777963248381,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Pediatric nonalcoholic fatty liver disease (NAFLD) is a growing problem, but its underlying mechanisms are poorly understood. We used transcriptomic reporter cell assays to investigate differences in transcriptional signatures induced in hepatocyte reporter cells by the sera of children with and without NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied serum samples from 45 children with NAFLD and 28 children without NAFLD. The sera were used to induce gene expression in cultured HepaRG cells and RNA\u2010sequencing was used to determine gene expression. Computational techniques were used to compare gene expression patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sera from children with NAFLD induced the expression of 195 genes that were significantly differentially expressed in hepatocytes compared to controls with obesity. NAFLD was associated with increased expression of genes promoting inflammation, collagen synthesis, and extracellular matrix remodeling. Additionally, there was lower expression of genes involved in endobiotic and xenobiotic metabolism, and downregulation of peroxisome function, oxidative phosphorylation, and xenobiotic, bile acid, and fatty acid metabolism. A 13\u2010gene signature, including upregulation of <jats:italic>TREM1<\/jats:italic> and <jats:italic>MMP1<\/jats:italic> and downregulation of <jats:italic>CYP2C9<\/jats:italic>, was consistently associated with all diagnostic categories of pediatric NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The extracellular milieu of sera from children with NAFLD induced specific gene profiles distinguishable by a hepatocyte reporter system. Circulating factors may contribute to inflammation and extracellular matrix remodeling and impair xenobiotic and endobiotic metabolism in pediatric NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpn3.12163","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T09:40:42Z","timestamp":1708681242000},"page":"886-897","source":"Crossref","is-referenced-by-count":2,"title":["A serum\u2010induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease"],"prefix":"10.1002","volume":"78","author":[{"given":"T.","family":"Hang Nghiem\u2010Rao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jethro S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington Connecticut USA"},{"name":"Oxford Centre for 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Diego School of Medicine University of California La Jolla California USA"},{"name":"Department of Pathology Sharp Medical Center San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pippa M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Quantitative Health Sciences Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary L.","family":"Holtz","sequence":"additional","affiliation":[{"name":"Center for Microbiome Research Medical College of Wisconsin Milwaukee Wisconsin USA"},{"name":"Department of Pediatrics, Division of Gastroenterology Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George M.","family":"Weinstock","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine Farmington Connecticut USA"},{"name":"Department of 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