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Although the number of patients is globally increasing and many clinical studies have developed medicine for MASLD, most of the studies have failed due to low efficacy. One reason for this failure is the lack of appropriate animal disease models that reflect human MASLD to evaluate the potency of candidate drugs. Methods: We developed a novel choline-deficient and 0.11%-methionine-added high-fat diet (CDAHFD)-based (MASH) diet that can induce murine metabolic-dysfunction-associated steatohepatitis (MASH) without severe body weight loss. We performed kinetic analyses post-feeding and proposed an appropriate timing of MASH pathogenesis by quantitatively analyzing steatosis, inflammation, and fibrosis. Results: This MASH diet induced liver fibrosis earlier than the conventional CDAHFD model. In brief, lipid accumulation, inflammation, and fibrosis started after 1 week from feeding. Lipid accumulation increased until 8 weeks and declined thereafter; on the other hand, liver fibrosis showed continuous progression. Additionally, immune cells, especially myeloid cells, specifically accumulated and induced inflammation in the initiation stage of MASH. Conclusions: The novel MASH diet promotes the dynamics of lipid deposition and fibrosis in the liver, similar to human MASH pathophysiology. Furthermore, immune-cell-derived inflammation possibly contributes to the initiation of MASH pathogenesis. We propose this model can be the new pre-clinical MASH model to discover the drugs against human MASH by evaluating the interaction between parenchymal and non-parenchymal cells.<\/jats:p>","DOI":"10.3390\/nu16234151","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T03:50:57Z","timestamp":1733111457000},"page":"4151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Choline-Deficient and 0.1%-Methionine-Added High-Fat Diet Induces Burned-Out Metabolic-Dysfunction-Associated Steatohepatitis with Inflammation by Rapid Immune Cell Infiltration on Male Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Takatoshi","family":"Sakaguchi","sequence":"first","affiliation":[{"name":"Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0662-5688","authenticated-orcid":false,"given":"Yasuharu","family":"Nagahama","sequence":"additional","affiliation":[{"name":"Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan"},{"name":"Host Defense Laboratory, Immunology Unit, Osaka Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Minoh 562-0029, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3464-1832","authenticated-orcid":false,"given":"Nanako","family":"Hamada","sequence":"additional","affiliation":[{"name":"Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1965-1759","authenticated-orcid":false,"given":"Shailendra Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Mikami","sequence":"additional","affiliation":[{"name":"Oriental Yeast Co., Ltd., Itabashi 174-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Maeda","sequence":"additional","affiliation":[{"name":"Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan"},{"name":"Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Laboratory of Host Defense, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan"},{"name":"Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita 565-0871, Japan"},{"name":"Center for Advanced Modalities and Drug Delivery System (CAMaD), Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The Global Epidemiology of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH): A Systematic Review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current Status and Future Trends of the Global Burden of MASLD","volume":"35","author":"Miao","year":"2024","journal-title":"Trends Endocrinol. 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