Potential to Cure Obesity-Related Asthma with Drugs?

asthmaLeptin, a hormone that plays a key role in energy metabolism, appetite, bone mass and fertility also regulates airway diameter, according a new study from Columbia University Medical Center.  This could explain why obese people are likely to have asthma and suggests that asthma associated with body weight may be treated with drugs.

When obesity develops in people with asthma, it worsens the breathing disorder and hinders its treatment through mechanisms that are not well understood.  One thing that is well documented is that obesity can cause narrowing of the airways (called bronchoconstriction). The new study’s goal was to shed light on the genetic and molecular basis of the connections among obesity, lung function, and airway diameter.

In an animal model, researchers demonstrated that both abnormally low and abnormally high body weight and fat mass result in narrowing of the airways and diminished lung function. Then they showed that independently of its regulation of appetite, leptin increases airway diameter.  It does so by reducing the activity of the parasympathetic nervous system – which is a part of the autonomic nervous system that’s not usually associated with leptin.  Additionally, the study found that regulation of airway diameter occurs regardless of local inflammation in the bronchi. Two further experiments were conducted in asthmatic mice. First, the researchers gave the mice a substance that increases lung inflammation. When they infused leptin in the brain of these mice for several days, there was no effect on inflammation; however, airway diameter and lung functions were normal.  Next, they gave obese, asthmatic mice drugs that decrease parasympathetic tone, (rate of neuronal firing).  The experiments showed that obesity-related asthma in mice can be cured without affecting inflammation. This implies that it might be possible to treat weight-related asthma with existing drugs that inhibit parasympathetic signaling — and thereby increase leptin-related brain signaling.  Further study is needed before these types of drugs can be recommended for obese people with asthma.

“This study is very interesting and important for the treatment of asthma in morbidly obese patients,” said Dr. Toby Broussard, expert weight loss surgeon in Oklahoma. “It provides the possibility of a much needed new treatment mechanism.  The effects of asthma can be difficult to control at times in morbidly obese patients and the hope of new therapies would be much welcomed in my practice.”

In 2012, researchers solved the challenging crystal structure of the leptin-binding domain of the obesity receptor using a technique called X-ray crystallography. This advancement enhanced the potential to generate drugs which can both block and stimulate the receptor for the obesity hormone leptin, which could potentially treat both obesity and malnutrition. You can read more about the study here.

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