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As transplanted human hepatocytes do not respond to mouse growth hormone (GH) and tend to accumulate fat, we hypothesized that addition of human GH would alter lipid metabolism and reduce accumulation of fat in the liver even when fed a high-fat diet. Six uPA\/SCID chimeric mice were fed a high-fat GAN diet to induce fatty liver while six were fed a normal CRF1 diet, and GH was administered to three mice in each group. The mice were euthanized at 8\u00a0weeks, and human hepatocytes were extracted for RNA-Seq, DIA proteomics, and metabolomics analysis. Abdominal echocardiography revealed that the degree of fatty liver increased significantly in mice fed GAN diet (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and decreased significantly in mice treated with GH (<jats:italic>p<\/jats:italic>\u2009=\u20090.026). Weighted gene correlation network analysis identified <jats:italic>IGF1<\/jats:italic> and <jats:italic>SEMA7A<\/jats:italic> as eigengenes. Administration of GH significantly reduced triglyceride levels and was strongly associated with metabolism of amino acids. MiBiOmics analysis identified perilipin-2 as a co-inertia driver. Results from multi-omics analysis revealed distinct gene expression and protein\/metabolite profiles in each treatment group when mice were fed a high-fat or normal diet with or without administration of GH.<\/jats:p>","DOI":"10.1038\/s41598-024-53890-8","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T15:02:45Z","timestamp":1707490965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multi-omics analysis of a fatty liver model using human hepatocyte chimeric mice"],"prefix":"10.1038","volume":"14","author":[{"given":"Akemi","family":"Ichikawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiki","family":"Miki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1691-3544","authenticated-orcid":false,"given":"C. 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PLoS One 10, e0142145. https:\/\/doi.org\/10.1371\/journal.pone.0142145 (2015).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53890-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53890-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53890-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T15:06:23Z","timestamp":1707491183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53890-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,9]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["53890"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-53890-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2024,2,9]]},"assertion":[{"value":"26 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Akemi Ichikawa is an employee of Pfizer, Inc. Chise Tateno and Yuji Ishida are employees of PhoenixBio. Kazuaki Chayama has consulted for AbbVie Inc,  Bristol-Myers Squibb, and Eisai and received research funding form Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Toray Industries, Inc, Takeda Pharmaceutical Company, Ajinomoto, Astellas, AstraZeneca, Eisai, GlaxoSmithKline, Janssen, Kowa, Kyorin, MSD, Nippon Kayaku, Nippon Seiyaku, Nippon Shinyaku, Roche, Teijin, Torii, Tsumura, Zeria, Daiichi Sankyo; and received payment for lectures from Mitsubishi Tanabe Pharma Corporation, MSD, Ajinomoto, Astellas, AstraZeneca, Bayer, Daiichi Sankyo, Dainippon Sumitomo Pharma, Bristol-Myers Squibb, GlaxoSmithKline KK, Chugai Pharmaceutical Co., Ltd, Eisai, Janssen, Kyorin, Meiji Seika, Toray Industries, Inc, Takeda Pharmaceutical Company, Torii, Zeria and Otsuka Pharmaceutical Co., Ltd. All other authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3362"}}