Substance P antagonist improves both obesity and asthma in a mouse model. Issue 1 (26th November 2012)

• Record Type: Journal Article
• Authors: Ramalho, R.; Almeida, J.; Beltrão, M.; Pirraco, A.; Costa, R.; Sokhatska, O.; Guardão, L.; Palmares, C.; Guimarães, J. T.; Delgado, L.; Moreira, A.; Soares, R.
• Is Part Of: Allergy. Volume 68:Issue 1(2013:Jan.)
• Page Start: 48
• Page End: 54
• Publication Date: 2012-11-26
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12052
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" xml:lang="en" id="all12052-abs-0001"> <title>Abstract</title> <sec id="all12052-sec-0001" sec-type="section"> <title>Background</title> <p>Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P (SP), involved in neurogenic inflammation by acting through its receptor NK1‐R, seems to participate in obese–asthma phenotype in mice.</p> </sec> <sec id="all12052-sec-0002" sec-type="section"> <title>Objectives</title> <p>To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet‐induced obesity and asthma.</p> </sec> <sec id="all12052-sec-0003" sec-type="section"> <title>Methods</title> <p>Diet‐induced obese Balb/c mice were sensitized and challenged with ovalbumin (OVA) and treated with a selective NK1‐R antagonist or placebo. Serum glucose, insulin, IL‐6, resistin, and OVA‐specific IgE levels were quantified. A score for peribronchial inflammation in lung histology was used. Cells were counted in bronchoalveolar lavage fluid. Adipocyte sizes were measured.</p> </sec> <sec id="all12052-sec-0004" sec-type="section"> <title>Results</title> <p>Ovalbumin‐obese mice treated with NK1‐R antagonist had lower weight (<italic>P</italic> = 0.0002), reduced daily food intake (<italic>P</italic> = 0.0021), reduced daily energy intake (<italic>P</italic> = 0.0021), reduced surface adipocyte areas (<italic>P</italic> < 0.0001), lower serum glucose (<italic>P</italic> = 0.04), lower serum insulin (<italic>P</italic> = 0.03), lower serum IL‐(<italic>P</italic> = 0.0022), lower serum resistin (<italic>P</italic> = 0.0043), lower serum OVA‐specific IgE (<italic>P</italic> = 0.035), and lower peribronchial inflammation score (<italic>P</italic> < 0.0001) than nontreated OVA‐obese mice. We observed an interaction between obesity, allergen sensitization, and treatment with NK1‐R antagonist for metabolic and systemic biomarkers, and for allergen sensitization and bronchial inflammation, showing a synergy between these variables.</p> </sec> <sec id="all12052-sec-0005" sec-type="section"> <title>Conclusion & Clinical Relevance</title> <p>In an experimental model of obesity and asthma in mice, NK1‐R blockade improved metabolic and systemic biomarkers, as well as allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese–asthma phenotype and highlight SP as a target with potential clinical interest in the obese–asthma epidemics.</p> </sec> </abstract>