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This study investigates the therapeutic potential of Flammulina velutipes immunomodulatory protein (FIP-fve) in a murine model of obesity-aggravated allergic asthma. BALB\/c mice were fed a high-fat diet (HFD) and sensitized with Dermatophagoides pteronyssinus (Der p) to induce obesity-associated allergic airway inflammation. FIP-fve was administered orally during the sensitization phase. Body weight, serum metabolic parameters (cholesterol, glucose, ALT), airway hyper-responsiveness (AHR), serum cytokine profiles, and lung histopathology were evaluated. FIP-fve treatment significantly reduced HFD-induced body weight gain and normalized serum cholesterol, glucose, and ALT levels. In the obese asthma model, FIP-fve markedly attenuated Der p-induced AHR and decreased serum levels of pro-inflammatory and allergic markers, including IL-6, IL-33, osteopontin, and VCAM-1. Cytokine array analysis revealed that FIP-fve reversed the upregulation of multiple inflammatory, metabolic, and angiogenic cytokines induced by HFD and allergen exposure. Histological analysis confirmed reduced inflammatory cell infiltration and tissue remodeling in the lungs of FIP-fve-treated mice. FIP-fve exhibits multi-targeted protective effects against obesity-aggravated allergic asthma by modulating systemic metabolism, suppressing airway inflammation, and regulating key cytokine networks. These findings suggest that FIP-fve holds promise as a novel therapeutic candidate for the management of obesity-related asthma and its associated metabolic dysfunction.<\/jats:p>","DOI":"10.1038\/s41598-025-18166-9","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:21:57Z","timestamp":1758806517000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fungal immunomodulatory protein FIP-fve mitigates airway inflammation and metabolic dysfunction in an obese allergic asthma model"],"prefix":"10.1038","volume":"15","author":[{"given":"Chang-Hung","family":"Hsiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiunn-Liang","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-Shuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ko-Huang","family":"Lue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Ta","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"18166_CR1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1097\/MCP.0000000000000446","volume":"24","author":"OA Carpaij","year":"2018","unstructured":"Carpaij, O. 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The animal experiment approval number is 2127.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics declarations"}}],"article-number":"32770"}}