Regulating airway diameter through leptin, which uses the parasympathetic tone to regulate airway diameter, made it possible for researchers to successfully correct bronchoconstriction in obese mice, according to new research published in the online edition of the journal Cell Metabolism.
Leptin is a hormone that plays a key role in energy metabolism, fertility, and bone mass. Its ability to regulate airway diameter 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, according to researchers.
“Our study started with the clinical observation that both obesity and anorexia can lead to asthma,” said the study’s lead author Gerard Karsenty MD, PhD, a professor of medicine and the chair of genetics and development at Columbia University Medical Center (CUMC). “This led us to suspect that there must be a signal coming from fat cells that somehow affects the lungs – directly or indirectly.”
In a mouse model, researchers showed that abnormally low or high body weight and fat mass results in bronchoconstriction and diminished lung function. They then demonstrated that leptin increases airway diameter independently of, and at a lower threshold than, its regulation of appetite.
Two experiments were conducted. In the first, obese, asthmatic mice were exposed a substance that increases lung inflammation. Researchers then 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,” Karsenty said. “This showed that, at least in the mouse, you can cure obesity-related asthma without affecting inflammation.”
In the second experiment, obese, asthmatic mice were administered drugs to parasympathetic tone, or rate of neuronal firing. The asthma abated after several days.
“The therapeutic implication is that it may be possible to correct asthma in obese people with drugs that inhibit parasympathetic signaling — and thereby increase leptin-related brain signaling,” said Karsenty, who noted that clinical trials are needed before existing drugs can be recommended for the treatment of body weight-associated asthma.