Obesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthma

Allergy. 2012 Dec;67(12):1519-29. doi: 10.1111/all.12031. Epub 2012 Sep 25.

Abstract

Background: Clinical and epidemiological studies show a close association between obesity and the risk of asthma development. The underlying cause-effect relationship between metabolism, innate and adaptive immunity, and inflammation remains to be elucidated.

Methods: We developed an animal model to study the interaction between metabolic abnormalities and experimentally induced asthma. Obesity-susceptible AKR mice were fed with high-fat diet (HFD) or normal low-fat diet (LFD) and subjected to a protocol of ovalbumin (OVA) sensitization and airway allergen challenges followed by assessment of inflammation and lung function.

Results: AKR mice developed obesity and a prestage of metabolic syndrome following HFD. This phenotype was associated with an increase in proinflammatory macrophages (CD11b+/CD11c+) together with higher serum levels of interleukin 6. Obese mice showed increased susceptibility to allergic sensitization as compared to LFD animals. Anti-ovalbumin IgE antibody titers correlated positively and anti-OVA IgG2a antibodies titers correlated negatively with body weight. Airway eosinophilia showed a positive correlation with body weight, whereas mucus production did not change with obesity.

Conclusions: This obesity model demonstrates that HFD-induced obesity lowers the sensitization threshold in a model of asthma. This finding helps to understand why, particularly during childhood, obesity is a risk factor for the development of allergic asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / complications
  • Asthma / immunology*
  • Asthma / metabolism
  • Diet, High-Fat
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Female
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lung / immunology
  • Lung / physiopathology
  • Mice
  • Obesity / complications
  • Obesity / immunology*
  • Obesity / metabolism
  • Pulmonary Eosinophilia / immunology*
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism