High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol

Autor(es)

Andre, Diana M. ^[1] ; Calixto, Marina C. ^[1] ; Sollon, Carolina ^[1] ; Alexandre, Eduardo C. ^[1] ; Tavares, Edith B. G. ^[1] ; Naime, Ana C. A. ^[1] ; Anhe, Gabriel F. ^[1] ; Antunes, Edson ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, DEC 11 2017.
• Citações Web of Science: 3

Resumo

Insulin resistance plays an important role in obesity-associated asthma exacerbations. 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 beta (IR beta) in lung tissue and isolated bronchi (p < 0.05), which were impaired in obese group. Instead, obese mice displayed increased tyrosine nitrations of AKT, IR beta and IRS-1 (p < 0.05). Two-week therapy of obese mice with resveratrol (100 mg/kg/day) restored insulin-stimulated AKT, IRS-1 and IR beta phosphorylations, and simultaneously blunted the tyrosine nitration of these proteins. Additionally, the c-Jun N-terminal kinase (JNK) and inhibitor of NF-kappa B Kinase (I kappa K) phosphorylations were significantly increased in obese group, an effect normalized by resveratrol. In separate experiments, the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (20 mg/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. (AU)

• Processo FAPESP: 14/02130-1 - Papel da resistência à insulina no recrutamento pulmonar de eosinófilos em camundongos obesos: potencial anti-inflamatório e antioxidante do resveratrol
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular