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Using a murine model of allergic airway inflammation, we evaluated the insulin signaling transmission in lungs of obese compared with lean mice. We further evaluated the effects of the polyphenol resveratrol in the pulmonary insulin signaling. In lean mice, insulin stimulation significantly increased phosphorylations of AKT, insulin receptor substrate 1 (IRS-1) and insulin receptor \u03b2 (IR\u03b2) in lung tissue and isolated bronchi (p\u2009&lt;\u20090.05), which were impaired in obese group. Instead, obese mice displayed increased tyrosine nitrations of AKT, IR\u03b2 and IRS-1 (p\u2009&lt;\u20090.05). Two-week therapy of obese mice with resveratrol (100\u2009mg\/kg\/day) restored insulin-stimulated AKT, IRS-1 and IR\u03b2 phosphorylations, and simultaneously blunted the tyrosine nitration of these proteins. Additionally, the c-Jun N-terminal kinase (JNK) and inhibitor of NF-\u03baB Kinase (I\u03baK) phosphorylations were significantly increased in obese group, an effect normalized by resveratrol. In separate experiments, the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (20\u2009mg\/kg\/day, three weeks) mimicked the protective effects exerted by resveratrol in lungs of obese mice. Lungs of obese mice display nitrosative-associated impairment of insulin signaling, which is reversed by resveratrol. Polyphenols may be putative drugs to attenuate asthma exacerbations in obese individuals.<\/jats:p>","DOI":"10.1038\/s41598-017-17558-w","type":"journal-article","created":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T05:38:31Z","timestamp":1512452311000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol"],"prefix":"10.1038","volume":"7","author":[{"given":"Diana M.","family":"Andr\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C.","family":"Calixto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Sollon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo C.","family":"Alexandre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith B. 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