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Systemic adipose tissue is thought to be a primary source of lipids and energy during this process; however, empirical data on the effects of adipose tissue deficiency are limited. This study investigates the role of adipose tissue in liver regeneration, focusing on transient regeneration\u2010associated steatosis (TRAS) and hepatocyte proliferation using a Seipin knockout mouse model that mimics severe human lipodystrophy. Additionally, the study explores therapeutic strategies through adipose tissue transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Seipin knockout (<jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) and wild\u2010type (WT) mice underwent 2\/3 partial hepatectomy (PHx). Liver and plasma samples were collected at various time points post\u2010surgery. Histological assessments, lipid accumulation analyses and measurements of hepatocyte proliferation markers were conducted. Additionally, normal adipose tissue was transplanted into <jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice to evaluate the restoration of liver regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice exhibited significantly reduced liver regeneration rates and impaired TRAS, as evidenced by histological and lipid measurements. While WT mice demonstrated extensive hepatocyte proliferation at 48 and 72\u00a0h post\u2010PHx, characterised by increased mitotic cells, elevated proliferating cell nuclear antigen and Ki67 expression, <jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice showed delayed hepatocyte proliferation. Notably, adipose tissue transplantation into <jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice restored TRAS and improved liver regeneration and hepatocyte proliferation. Conversely, liver\u2010specific overexpression of Seipin in <jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice did not affect TRAS or liver regeneration, indicating that the observed effects are primarily due to adipose tissue deficiency rather than hepatic Seipin itself.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Systemic adipose tissue is essential for TRAS and effective liver regeneration following PHx. Its deficiency impairs these processes, while adipose tissue transplantation can restore normal liver function. These findings underscore the critical role of adipose tissue in liver recovery and suggest potential therapeutic strategies for liver diseases associated with lipodystrophies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice, which lack adipose tissue, exhibit significantly impaired TRAS and delayed liver regeneration following partial hepatectomy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Transplantation of normal adipose tissue into <jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice restores TRAS and enhances liver regeneration, highlighting the essential role of adipose tissue in these processes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Liver\u2010specific overexpression of Seipin has no effect on TRAS and liver regeneration in <jats:italic>Seipin<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70238","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T23:39:21Z","timestamp":1740094761000},"source":"Crossref","is-referenced-by-count":4,"title":["Adipose tissue deficiency impairs transient lipid accumulation and delays liver regeneration following partial hepatectomy in male Seipin knockout mice"],"prefix":"10.1002","volume":"15","author":[{"given":"Qianqian","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology The Key Laboratory of Neural and Vascular Biology Ministry of Education, The Key Laboratory of Vascular Biology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University  Shijiazhuang Hebei China"},{"name":"Department of Clinical Laboratory The Second Hospital of Hebei Medical University  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