Format

Send to

Choose Destination
Cell Metab. 2013 Jan 8;17(1):35-48. doi: 10.1016/j.cmet.2012.12.004.

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

Author information

1
Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Erratum in

  • Cell Metab. 2013 Mar 5;17(3):463-4.

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 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.

PMID:
23312282
PMCID:
PMC3815545
DOI:
10.1016/j.cmet.2012.12.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center