Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma.
Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma.
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DOI：
10.1016/j.cmet.2012.12.004
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发表时间：
2013-01-08
期刊：
影响因子：
29
通讯作者：
Karsenty G
中科院分区：
文献类型：
--
作者：
Arteaga-Solis E;Zee T;Emala CW;Vinson C;Wess J;Karsenty G
无论体重异常高或低，都经常观察到由气道直径减小（支气管收缩）引起的肺功能受损。这些相反的条件影响气道类似地表明气道直径和体重的调节是交织在一起的。我们在这里表明，独立于其调节食欲，黑皮质素途径，或交感神经紧张，瘦素是必要的和足够的增加气道直径的信号通过其同源受体在胆碱能神经元。后者通过气道平滑肌细胞中的M3毒蕈碱受体减少副交感神经信号传导，从而增加气道直径而不影响局部炎症。因此，降低副交感神经张力遗传或非遗传性地纠正支气管收缩并使肥胖小鼠的肺功能正常化，而与支气管炎症无关。这项研究揭示了脂肪细胞依赖性的调节支气管直径的破坏有助于肺功能受损所造成的体重异常。这些发现可能对肥胖相关性哮喘的治疗有帮助。
Impaired lung function caused by decreased airway diameter (bronchoconstriction) is frequently observed whether body weight is abnormally high or low. That these opposite conditions affect the airways similarly suggests that the regulation of airway diameter and body weight are intertwined. We show here that, independently of its regulation of appetite, melanocortin pathway, or sympathetic tone, leptin is necessary and sufficient to increase airway diameter by signaling through its cognate receptor in cholinergic neurons. The latter decreases parasympathetic signaling through the M3 muscarinic receptor in airway smooth muscle cells, thereby increasing airway diameter without affecting local inflammation. Accordingly, decreasing parasympathetic tone genetically or pharmacologically corrects bronchoconstriction and normalizes lung function in obese mice regardless of bronchial inflammation. This study reveals an adipocyte-dependent regulation of bronchial diameter whose disruption contributes to the impaired lung function caused by abnormal body weight. These findings may be of use in the management of obesity-associated asthma.
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影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
DOI：
10.1016/j.jaci.2011.06.009
发表时间：
2011-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Dixon AE;Pratley RE;Forgione PM;Kaminsky DA;Whittaker-Leclair LA;Griffes LA;Garudathri J;Raymond D;Poynter ME;Bunn JY;Irvin CG
通讯作者：
Irvin CG
影响因子：
15.9
作者：
Bjornholm, Marie;Munzberg, Heike;Myers, Martin G., Jr.
通讯作者：
Myers, Martin G., Jr.
DOI：
10.1165/rcmb.2007-0091oc
发表时间：
2008-10-01
影响因子：
6.4
作者：
Nair, Paranneswaran;Radford, Katherine;Cox, P. Gerard
通讯作者：
Cox, P. Gerard
影响因子：
5.8
作者：
Mantzoros, C;Flier, JS;Jimerson, DC
通讯作者：
Jimerson, DC