A study reveals that leptin, a hormone that plays a key role in energy metabolism, fertility and bone mass, also regulates the diameter of the airways. The study was led by researchers at Columbia University (USA).
The findings could explain why obese people are prone to asthma and suggest that body weight-associated asthma may be relieved with medications that inhibit signaling through the parasympathetic nervous system, which mediates leptin function.
"Our study started with the clinical observation that both obesity and anorexia can lead to asthma," said Gerard Karsenty MD, PhD, professor and chair of genetics and development and professor of medicine at CUMC, and lead author of the study. "This led us to suspect that there must be a signal coming from fat cells that somehow affects the lungs -directly or indirectly." The most likely candidate was leptin, a protein made by fat cells that circulates in the bloodstream and travels to the brain.
Extensive evidence shows that obesity can cause narrowing of the airways (bronchoconstriction). When obesity develops in people with asthma, it exacerbates the breathing disorder and hampers its treatment through mechanisms that are poorly understood. The current study was designed to elucidate the genetic and molecular bases of the relationships among obesity, airway diameter, and lung function.
Through mouse studies, the researchers showed that abnormally low or high body weight and fat mass results in bronchoconstriction and diminished lung function. Next, they showed that leptin increases airway diameter independently of, and at a lower threshold than, its regulation of appetite.
Leptin affects the airways by decreasing the activity of the parasympathetic nervous system, a branch of the autonomic nervous system not usually associated with leptin. The researchers also showed that regulation of airway diameter occurs regardless of local inflammation in the bronchi.
The researchers conducted two subsequent experiments to determine if these findings might have bearing on asthma therapy. In one, they took obese, asthmatic mice and administered a substance that increases lung inflammation. When they infused leptin in the brain of these mice for four days, "There was no effect on inflammation, but airway diameter and lung functions were normal," said Dr. Karsenty. "This showed that, at least in the mouse, you can cure obesity-related asthma without affecting inflammation."
In the second experiment, the researchers treated obese, asthmatic mice with drugs that decrease parasympathetic tone, or rate of neuronal firing. Again, the asthma abated after several days.
The study has been published in the online edition of the journal Cell Metabolism.