Vitamin D binding protein induces skeletal muscle atrophy and contributes to cancer-associated muscle wasting

Vitamin D binding protein induces skeletal muscle atrophy and contributes to cancer-associated muscle wasting | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Vitamin D binding protein induces skeletal muscle atrophy and contributes to cancer-associated muscle wasting Nicoletta Filigheddu, Tommaso Raiteri, Simone Reano, Andrea Scircoli, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4289125/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The maintenance of skeletal muscle is of pivotal importance, as its loss is often associated with progressive pathologies, generally worsening the prognosis. Increased levels of vitamin D binding protein (VDBP) were reported in diseases susceptible to muscle wasting, including several tumors. We hypothesized that VDBP might participate in muscle wasting and investigated its direct effects on skeletal muscle homeostasis. Here we demonstrate that VDBP induces atrophy independently of vitamin D. In C2C12 myotubes, we identified intracellular actin dynamics perturbation and subsequent mitochondrial dysfunction as the main molecular mechanisms of VDBP-induced atrophy. Coherently, the ectopic introduction of VDBP in mice lacking the protein (Gc-knockout mice) induced muscle atrophy and decreased strength. Finally, we present proof-of-concept evidence that VDBP contributes to cancer-associated muscle wasting. Altogether, these findings provide novel insights into the biological function of VDBP as a pro-atrophic hormone with potential implications for the treatment of muscle wasting. Biological sciences/Cell biology/Mechanisms of disease Biological sciences/Physiology/Metabolism/Homeostasis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS1.xlsx Proteomics 18h TableS2.xlsx Proteomics 24h TableS3.xlsx RNAseq Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4289125","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":299110122,"identity":"991327e5-214c-4dff-a655-5e296bd78e25","order_by":0,"name":"Nicoletta 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