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Several lines of evidence have shown that FSTL1 is essential for white adipose tissue (WAT) adipogenesis, brown adipose tissue involution, and thermogenesis. However, the roles of FSTL1 in WAT browning and its underlying mechanisms are not fully understood. Our data show that FSTL1 overexpression induces WAT browning, enhances energy metabolism, and promotes glucose uptake in male mice at ambient room temperature. Overexpression of FSTL1 specifically in WAT prevents metabolic dysfunction in mice with diet\u2010induced obesity. Mice with FSTL1 deficiency exhibit cold intolerance and are prone to obesity. FSTL1 cannot directly induce adipocyte browning in vitro. FSTL1 promotes sympathetic innervation both in vivo and in vitro. Furthermore, sympathetic denervation in adipose tissue abrogates FSTL1\u2010induced browning, enhancement of energy metabolism, and regional glucose uptake. Notably, FSTL1 is endocytosed by sympathetic neurons primarily via tropomyosin\u2010related kinase B (TrkB) in vitro. Blocking TrkB suppresses WAT browning and sympathetic innervation induced by FSTL1 overexpression in adipose tissue. Our findings shed new light on the role of FSTL1 in WAT browning and identify FSTL1 as an adipose\u2010derived \u2018neurotrophic factor\u2019 adipokine.<\/jats:p>","DOI":"10.1002\/advs.77433","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:20:32Z","timestamp":1788236432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Adipose\u2010Sympathetic Nerve Crosstalk: FSTL1 as an Adipocyte\u2010Derived Neurotrophic Factor for WAT Browning"],"prefix":"10.1002","author":[{"given":"Xiao\u2010Wei","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Human Anatomy School of Basic Medical Sciences Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy School of Basic Medical Sciences Capital Medical 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