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We established and compared four mouse models based on distinct pathogenic mechanisms. In the high-fat diet (HFD)-fed model, pancreatic steatosis occurred later than hepatic steatosis. In ob\/ob mice, despite severe obesity and hepatic steatosis, no significant intrapancreatic fat deposition was observed. In the caerulein combined with HFD model, caerulein markedly accelerated HFD-induced intrapancreatic fat accumulation, indicating a synergistic effect of inflammation and metabolic stress. Orthotopic injection of adipogenically differentiated 3T3-L1 cells established a focal model without altering systemic metabolism, enabling investigation of localized fat deposition. Collectively, these four models recapitulate metabolic, genetic, inflammatory, and localized mechanisms, exhibit divergent histological features, and provide a complementary platform for mechanistic studies and drug screening in pancreatic steatosis.<\/jats:p>","DOI":"10.3390\/ijms27104255","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Establishment and Comparative Analysis of Four Mouse Models for the Study of Pancreatic Steatosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4512-1287","authenticated-orcid":false,"given":"Xinpeng","family":"Yin","sequence":"first","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 102602, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 102602, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxue","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 102602, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 102602, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 102602, China"},{"name":"National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 102602, China"},{"name":"National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41574-021-00573-3","article-title":"Metabolic implications of pancreatic fat accumulation","volume":"18","author":"Wagner","year":"2022","journal-title":"Nat. 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