High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol.
High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol.
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DOI：
10.1038/s41598-017-17558-w
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发表时间：
2017-12-11
影响因子：
4.6
通讯作者：
Antunes E
中科院分区：
文献类型：
--
作者：
André DM;Calixto MC;Sollon C;Alexandre EC;Tavares EBG;Naime ACA;Anhê GF;Antunes E
胰岛素抵抗在肥胖相关性哮喘急性发作中起重要作用。使用过敏性气道炎症的小鼠模型，我们评估了肥胖小鼠与瘦小鼠肺中胰岛素信号传导的比较。我们进一步评估了多酚白藜芦醇在肺胰岛素信号转导中的作用。瘦鼠肺组织和离体支气管中AKT、胰岛素受体底物1（IRS-1）和胰岛素受体β（IRβ）磷酸化水平明显升高（p < 0.05），而肥胖鼠肺组织和离体支气管中AKT、IRS-1和IR β磷酸化水平明显降低（p < 0.05）。相反，肥胖小鼠显示AKT、IRβ和IRS-1的酪氨酸硝化增加（p < 0.05）。用白藜芦醇（100 mg/kg/天）治疗肥胖小鼠两周，恢复了胰岛素刺激的AKT、IRS-1和IRβ磷酸化，同时减弱了这些蛋白质的酪氨酸硝化。此外，肥胖组c-Jun N-末端激酶（JNK）和NF-κB激酶抑制剂（IκK）磷酸化显著增加，白藜芦醇使其正常化。在单独的实验中，诱导型一氧化氮合酶（iNOS）抑制剂氨基胍（20毫克/公斤/天，三周）模仿白藜芦醇在肥胖小鼠肺中发挥的保护作用。肥胖小鼠的肺显示出与亚硝化相关的胰岛素信号传导障碍，白藜芦醇可以逆转。多酚可能是减轻肥胖个体哮喘恶化的假定药物。
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 β (IRβ) in lung tissue and isolated bronchi (p < 0.05), which were impaired in obese group. Instead, obese mice displayed increased tyrosine nitrations of AKT, IRβ 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 IRβ phosphorylations, and simultaneously blunted the tyrosine nitration of these proteins. Additionally, the c-Jun N-terminal kinase (JNK) and inhibitor of NF-κB Kinase (IκK) 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.
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影响因子：
7.7
作者：
Karlsson, HKR;Zierath, JR;Wallberg-Henriksson, H
通讯作者：
Wallberg-Henriksson, H
影响因子：
2
作者：
Chang, Chih-Chun;Lin, Keng-Yang;Hung, Li-Man
通讯作者：
Hung, Li-Man
影响因子：
1.9
作者：
Al-Shawwa, Baha A.;Al-Huniti, Nidal H.;Gershan, William
通讯作者：
Gershan, William
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.
影响因子：
3.7
作者：
Barger JL;Kayo T;Vann JM;Arias EB;Wang J;Hacker TA;Wang Y;Raederstorff D;Morrow JD;Leeuwenburgh C;Allison DB;Saupe KW;Cartee GD;Weindruch R;Prolla TA
通讯作者：
Prolla TA