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- Title
Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness.
- Authors
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
- Abstract
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.
- Subjects
LUNGS; CHOLECYSTOKININ; SMOOTH muscle contraction; HORMONE receptors; ASTHMATICS; INTRANASAL administration; WEIGHT loss; ENTEROENDOCRINE cells
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35739-8