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Lipodystrophy syndromes are estimated to affect 1 in 20,000 people and are associated with metabolic comorbidities. Recently, we showed that fibrosis\u2010associated lipodystrophy depended on sustained Wnt signaling, although the mechanism remains unclear. Transcriptomic profiling of mature dermal adipocytes\n                    <jats:italic>in vivo<\/jats:italic>\n                    revealed that Wnt activation downregulated the\n                    <jats:italic>de novo<\/jats:italic>\n                    lipogenesis (DNL) axis enzymes within 48\u2009h. We further found that expression of fatty acid synthase (FASN), a key DNL enzyme, depends on sustained Wnt activation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In a bleomycin model, and in human systemic sclerosis (&lt;\u20091\u2009year disease duration) and keloids, FASN was significantly downregulated. Notably, inhibition of FASN in mice during reversal of Wnt\u2010induced fibrosis impaired the recovery of DWAT lipid content and ECM architecture. Collectively, these findings demonstrate that acquired lipodystrophy in skin fibrosis is mediated by a previously unrecognized role of the Wnt\u2013DNL axis. These findings underscore the importance of this pathway in lipodystrophy and fibrosis and highlight its potential as a therapeutic target in skin fibrosis. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70086","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:41:09Z","timestamp":1781606469000},"page":"98-113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lipodystrophy and adipose tissue recovery are mediated by the Wnt\/lipogenesis axis during skin fibrosis"],"prefix":"10.1002","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-585X","authenticated-orcid":false,"given":"Suneeti 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