title: Substance P antagonist improves both obesity and asthma in a mouse model.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet-induced obesity and asthma.
  
  
  METHODS
  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.
  
  
  RESULTS
  Ovalbumin-obese mice treated with NK1-R antagonist had lower weight (P = 0.0002), reduced daily food intake (P = 0.0021), reduced daily energy intake (P = 0.0021), reduced surface adipocyte areas (P < 0.0001), lower serum glucose (P = 0.04), lower serum insulin (P = 0.03), lower serum IL-(P = 0.0022), lower serum resistin (P = 0.0043), lower serum OVA-specific IgE (P = 0.035), and lower peribronchial inflammation score (P < 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunology, Faculty of Medicine, University of Porto, 4200 Porto, Portugal. rrenata@med.up.pt
authors.forename: R
authors.initials: R
authors.lastname: Ramalho
authors.forename: J
authors.initials: J
authors.lastname: Almeida
authors.forename: M
authors.initials: M
authors.lastname: Beltrão
authors.forename: A
authors.initials: A
authors.lastname: Pirraco
authors.forename: R
authors.initials: R
authors.lastname: Costa
authors.forename: O
authors.initials: O
authors.lastname: Sokhatska
authors.forename: L
authors.initials: L
authors.lastname: Guardão
authors.forename: C
authors.initials: C
authors.lastname: Palmares
authors.forename: J T
authors.initials: JT
authors.lastname: Guimarães
authors.forename: L
authors.initials: L
authors.lastname: Delgado
authors.forename: A
authors.initials: A
authors.lastname: Moreira
authors.forename: R
authors.initials: R
authors.lastname: Soares
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology; D001991:Bronchitis / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
chemical_list: D000485:Allergens; D015415:Biomarkers; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P