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Both the thyroid hormone receptor \u03b21 (TR\u03b2) and peroxisome proliferator\u2010activated receptor gamma coactivator 1\u2010alpha (PGC1\u03b1) are key regulators of mitochondrial function and lipid metabolism. However, their specific interaction and influence on ccRCC development and lipid accumulation remain poorly understood. This\u00a0study\u00a0identified\u00a0genes\u00a0jointly\u00a0regulated by TR\u03b2 and PGC1\u03b1, which are implicated in lipid browning and mitochondrial fusion. Mechanistically, T3\u2010activated TR\u03b2 interacts with PGC1\u03b1 to transcriptionally upregulate PGC1\u03b1, UCP1, and mitochondrial fusion genes OPA1 and MFN2, thereby enhancing mitochondrial activity, promoting lipid utilization, and suppressing ccRCC progression. These results indicate that the mitochondrial and metabolic effects of TR\u03b2 in ccRCC are mediated through PGC1\u03b1 expression and function. Activation of the TR\u03b2\/PGC1\u03b1 through hormonal and pharmacological means may offer a promising therapeutic approach for ccRCC.<\/jats:p>","DOI":"10.1002\/advs.202508571","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:09:04Z","timestamp":1762754944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Thyroid Hormone Receptor \u03b21 and PGC1\u03b1 Coordinately Regulate OPA1\/MFN2\u2010Mediated Mitochondrial Fusion and UCP1\u2010Mediated Lipid Browning in ccRCC"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiangui","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518000 China"},{"name":"Institute of Urology Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiexi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518000 China"},{"name":"Institute of Urology Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518000 China"},{"name":"Institute of Urology Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiquan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518000 China"},{"name":"Institute of Urology Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology  Wuhan 430030 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518000 China"},{"name":"Institute of Urology Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-7157","authenticated-orcid":false,"given":"Wen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"},{"name":"Shenzhen Huazhong University of Science and Technology Research Institute  Shenzhen 518000 China"},{"name":"Institute of Urology Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.04.002"},{"key":"e_1_2_11_2_1","first-page":"184","volume":"14","author":"Lazar M. 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