{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:51:30Z","timestamp":1785433890696,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,25]]},"group-title":"Cell Biology","reference-count":76,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["AR076938"],"award-info":[{"award-number":["AR076938"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019921","name":"National Scleroderma Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019921","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Acquired lipodystrophy in the dermal white adipose tissue (DWAT) is a salient feature of skin fibrosis, and is followed by accumulation of extracellular matrix (ECM). Lipodystrophy syndromes, often associated with metabolic co-morbidities, are estimated to affect 1 in 20,000 people. We recently showed that fibrosis-associated lipodystrophy is dependent on sustained Wnt signaling, but the mechanism is unclear. Transcriptomic profiling of mature dermal adipocytes\n                  <jats:italic>in vivo<\/jats:italic>\n                  reveal that Wnt activation downregulates the\n                  <jats:italic>de novo<\/jats:italic>\n                  -lipogenesis (DNL) axis enzymes within 48 hours. We found that protein expression of Fatty Acid Synthase (FASN), a key DNL enzyme, is dependent on sustained Wnt activation\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  . In human systemic sclerosis,\n                  <jats:italic>FASN<\/jats:italic>\n                  mRNA is significantly downregulated during two years of disease. Remarkably, pharmacological inhibition of FASN enzyme during reversal from Wnt induced fibrosis impedes recovery of DWAT lipid content as well as ECM accumulation and topography. All together, we demonstrate that acquired lipodystrophy in the context of skin fibrosis is mediated by a new role of the Wnt-DNL axis. These findings underscore the importance of this pathway in lipodystrophy and fibrosis, opening new avenues for therapeutic targets in skin fibrosis.\n                <\/jats:p>","DOI":"10.1101\/2025.09.24.678215","type":"posted-content","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T21:45:14Z","timestamp":1758836714000},"source":"Crossref","is-referenced-by-count":0,"title":["Lipodystrophy and recovery are mediated by the Wnt\/lipogenesis axis during skin fibrosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-585X","authenticated-orcid":false,"given":"Suneeti","family":"Madhavan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-2567","authenticated-orcid":false,"given":"Piper","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-3675","authenticated-orcid":false,"given":"Rohan","family":"Varshney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5327-2806","authenticated-orcid":false,"given":"Miles","family":"Montegut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4438-8133","authenticated-orcid":false,"given":"Qiannan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-0152","authenticated-orcid":false,"given":"Kayla","family":"Klatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-7450","authenticated-orcid":false,"given":"Reshmi","family":"Parameswaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-212X","authenticated-orcid":false,"given":"Michael C.","family":"Rudolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-6552","authenticated-orcid":false,"given":"Radhika P.","family":"Atit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025092905350677000_2025.09.24.678215v1.1","unstructured":"Akinci B , et. al. Lipodystrophy Syndromes: Presentation and Treatment. In: Feingold KR , Anawalt B , Blackman MR , et al., eds. Endotext. MDText.com, Inc.; 2000. 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