Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness.
Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness.
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DOI：
10.1038/s41467-022-35739-8
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发表时间：
2023-01-04
影响因子：
16.6
通讯作者：
Lu, Quan
中科院分区：
文献类型：
--
作者：
Panganiban, Ronald Allan M.;Yang, Zhiping;Sun, Maoyun;Park, Chan Young;Kasahara, David I.;Schaible, Niccole;Krishnan, Ramaswamy;Kho, Alvin T.;Israel, Elliot;Hershenson, Marc B.;Weiss, Scott T.;Himes, Blanca E.;Fredberg, Jeffrey J.;Tantisira, Kelan G.;Shore, Stephanie A.;Lu, Quan
肥胖会增加哮喘的患病率和严重程度。然而，其潜在机制知之甚少，因此，肥胖哮喘患者的治疗选择仍然有限。在这里，我们报告，胆囊收缩素-代谢激素最有名的信号饱和脂肪代谢的作用，是增加在肥胖小鼠的肺和胆囊收缩素A受体信号的药理学阻断降低肥胖相关的气道高反应性。激素激活胆囊收缩素A受体可诱导气道平滑肌细胞收缩。在体内，胆囊收缩素水平在遗传和饮食诱导的肥胖小鼠的肺中升高。重要的是，鼻内给药胆囊收缩素A受体拮抗剂（丙谷胺和devazepide）抑制肥胖小鼠的气道高反应性。总之，我们的研究结果揭示了胆囊收缩素在肺中的意想不到的作用，并支持胆囊收缩素A受体拮抗剂作为肥胖哮喘患者的潜在治疗方法的再利用。肥胖如何增加哮喘患病率和严重程度的潜在机制还不清楚。在这里，作者表明，拮抗胆囊收缩素及其受体，CCKAR，在肺减弱肥胖相关的小鼠气道高反应性。
Obesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin—a metabolic hormone best known for its role in signaling satiation and fat metabolism—is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness. Activation of cholecystokinin A receptor by the hormone induces contraction of airway smooth muscle cells. In vivo, cholecystokinin level is elevated in the lungs of both genetically and diet-induced obese mice. Importantly, intranasal administration of cholecystokinin A receptor antagonists (proglumide and devazepide) suppresses the airway hyperresponsiveness in the obese mice. Together, our results reveal an unexpected role for cholecystokinin in the lung and support the repurposing of cholecystokinin A receptor antagonists as a potential therapy for asthma patients with obesity. The underlying mechanisms of how obesity increases asthma prevalence and severity are not well understood. Here, the authors show that antagonizing cholecystokinin and its receptor, CCKAR, in the lung attenuates obesity-associated airway hyperresponsiveness in mice.
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影响因子：
29
作者：
Arteaga-Solis E;Zee T;Emala CW;Vinson C;Wess J;Karsenty G
通讯作者：
Karsenty G
DOI：
10.1164/ajrccm.158.supplement_2.13tac110
发表时间：
1998-11-01
影响因子：
24.7
作者：
Johnson, M
通讯作者：
Johnson, M
影响因子：
3.3
作者：
Hussain, AA;Dakkuri, A;Hussain, MA
通讯作者：
Hussain, MA
影响因子：
24.3
作者：
Fricker, Michael;Gibson, Peter G.
通讯作者：
Gibson, Peter G.
影响因子：
1.9
作者：
Dixon, Anne E.;Shade, David M.;Wise, Robert A.
通讯作者：
Wise, Robert A.