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Maintaining precise regulation of adipogenesis and lipid metabolism in WAT is essential for systemic energy balance and metabolic health. Here, we identify Ssu72 phosphatase as a critical regulator of adipogenesis required for WAT expansion. Ssu72 expression is elevated in obese WAT. Notably, adipocyte-specific deletion of Ssu72 in mice confers resistance to high-fat diet (HFD)-induced obesity, accompanied by improved insulin sensitivity and altered energy expenditure. Ssu72 deficiency diminishes HFD-induced adipocyte hypertrophy and inflammation in WAT. Mechanistically, loss of Ssu72 inhibits PPAR\u03b3-mediated adipogenesis and lipid storage by hyperphosphorylation of GSK3\u03b2, resulting in suppression of WAT expansion. In addition, metabolic alterations in Ssu72-deleted WAT are reversed by restoring Ssu72 expression. Taken together, our findings reveal a novel adipocyte Ssu72-GSK3\u03b2 axis that regulates obesogenic adipogenesis in white adipocytes, suggesting that Ssu72 is a promising target for controlling diet-induced obesity and whole-body metabolic homeostasis.<\/jats:p>","DOI":"10.1038\/s41418-026-01799-2","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:30:13Z","timestamp":1782901813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ssu72 phosphatase orchestrates obesogenic adipogenesis and metabolic homeostasis during nutrient excess"],"prefix":"10.1038","author":[{"given":"Si","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-1672","authenticated-orcid":false,"given":"Joon-Sup","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0954-8649","authenticated-orcid":false,"given":"Eun-Ji","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehna Paula","family":"Ginting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Woo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gia Cac","family":"Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-5699","authenticated-orcid":false,"given":"Min-Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myong-Joon","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hee","family":"Um","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-1646","authenticated-orcid":false,"given":"Chang-Woo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"1799_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1188844","volume":"11","author":"U White","year":"2023","unstructured":"White U. 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