Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma.

ABSTRACT: 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 M(3) muscarinic receptor in airway smooth muscle cells, thereby increasing airway diameter without affecting local inflammation. Accordingly, decreasing parasympathetic tone genetically or pharmacologically correc

SUBMITTER: Arteaga-Solis E 

PROVIDER: S-EPMC3815545 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature