Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma.
Nitroalkene fatty acids modulate bile acid metabolism and lung function in obese asthma.
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DOI：
10.1038/s41598-021-96471-9
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发表时间：
2021-09-07
影响因子：
4.6
通讯作者：
Wendell SG
中科院分区：
文献类型：
--
作者：
Manni ML;Heinrich VA;Buchan GJ;O'Brien JP;Uvalle C;Cechova V;Koudelka A;Ukani D;Rawas-Qalaji M;Oury TD;Hart R;Ellgass M;Mullett SJ;Fajt ML;Wenzel SE;Holguin F;Freeman BA;Wendell SG
患有哮喘的肥胖个体的胆汁酸谱发生改变。因此，我们试图更好地了解如何肥胖相关的全身变化有助于肺病理生理学。我们还测试了硝基油酸（NO2-OA）的治疗潜力，代谢和炎症信号通路的调节剂，以减轻过敏原和肥胖诱导的哮喘小鼠模型肺功能下降。测定了健康受试者和哮喘患者的血浆以及过敏性气道疾病（AAD）和非过敏性气道疾病（AAD）小鼠的血清和肺组织中的胆汁酸。在用媒介物或NO2-OA治疗的患有屋尘螨诱导的AAD的肥胖小鼠中测量肺功能、炎症指数和肝胆汁酸酶表达。甘氨胆酸和甘氨熊去氧胆酸的血清水平在临床上与体重指数和气道高反应性相关，而β-鼠胆酸和牛磺-β-鼠胆酸的鼠水平显著升高，并与患有AAD的肥胖小鼠的肺功能受损呈正相关。NO2-OA通过调节胆汁酸合成酶的肝脏表达降低小鼠胆汁酸水平，同时降低小气道阻力和组织弹性。胆汁酸与体重指数和肺功能下降相关，硝基烯烃的信号传导作用可通过调节胆汁酸代谢限制AAD，揭示了改善当前标准治疗的潜在药理学方法。
Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of β-muricholic acid and tauro-β-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.
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影响因子：
8
作者：
通讯作者：
--
影响因子：
14.2
作者：
Crestani, Elena;Harb, Hani;Chatila, Talal A.
通讯作者：
Chatila, Talal A.
DOI：
10.4049/jimmunol.1501531
发表时间：
2016-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Manni ML;Mandalapu S;McHugh KJ;Elloso MM;Dudas PL;Alcorn JF
通讯作者：
Alcorn JF
DOI：
10.1016/j.jaci.2011.03.036
发表时间：
2011-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Holguin F;Bleecker ER;Busse WW;Calhoun WJ;Castro M;Erzurum SC;Fitzpatrick AM;Gaston B;Israel E;Jarjour NN;Moore WC;Peters SP;Yonas M;Teague WG;Wenzel SE
通讯作者：
Wenzel SE
DOI：
10.1016/j.jaci.2011.02.042
发表时间：
2011-08
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Moore WC;Evans MD;Bleecker ER;Busse WW;Calhoun WJ;Castro M;Chung KF;Erzurum SC;Curran-Everett D;Dweik RA;Gaston B;Hew M;Israel E;Mayse ML;Pascual RM;Peters SP;Silveira L;Wenzel SE;Jarjour NN;National Heart, Lung, and Blood Institute's Severe Asthma Research Group
通讯作者：
National Heart, Lung, and Blood Institute's Severe Asthma Research Group