Responses to ozone are increased in obese mice

Abstract

Epidemiological data indicate an increased incidence of asthma in overweight adults and children. Ozone (O3) is a common trigger for asthma. Accordingly, the purpose of this study was to compare O3-induced airway hyperresponsiveness and airway inflammation in lean, wild-type (C57BL/6J) mice and mice that are obese as a consequence of a genetic defect in the gene encoding the satiety hormone leptin (ob/ob mice). The ob/ob mice eat excessively and weighed more than twice as much as age- and gender-matched wild-type mice. Airway responsiveness to intravenous methacholine was measured by forced oscillation. In air-exposed controls, baseline pulmonary resistance was greater, and the dose of methacholine required to double pulmonary resistance was lower in ob/ob than wild-type mice. Exposure to O3 (2 parts/million for 3 h) caused AHR and airway inflammation in both groups of mice, but responses to O3 were enhanced in ob/ob compared with wild-type mice. Administration of exogenous leptin did not reverse the enhanced inflammatory response observed in ob/ob mice, but augmented airway inflammation in wild-type mice. The inhaled dose of O3 per gram of lung tissue was greater in ob/ob than wild-type mice. Our results indicate that O3-induced airway responses are enhanced in ob/ob mice and suggest that inhaled O3 dose may be one factor contributing to this difference, but other aspects of the obese phenotype may also contribute. Our results also indicate that the hormone leptin, which is increased in the obese, has the capacity to increase airway inflammation.

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

“…A similar result was found in the Normative Aging Study (9). Several experimental studies in mice have identified augmented responses to ozone in obese animals (26,27). A recent experimental study in mice found that adiponectin, which is deficient in the obese, protects against the inflammatory effects of ozone exposure (31).…”

Obesity, Nutrition, and Asthma in Children

“…Largely through the work of Shore et al, molecular and physiologic characteristics of the murine model of obese asthma are currently being elucidated. 23,[26][27][28][29][30][31][32][33][34] However, assessing lung inflammation and lung responses among obese children remains challenging and limited by current technologies. Studies in children involving bronchodilator responsiveness, bronchoconstricting agonists (e.g., methacholine challenge), and airway inflammatory markers have yet to show the same consistent pattern of hyperresponsiveness that have been demonstrated in mice.…”

Obesity induced bronchopulmonary hyperresponsiveness in Tunisian women

“…Further evidence of a direct association between obesity and airway hyperreactivity has been shown in an experimental study in which ozone-induced airway hyperreactivity and bronchial inflammation in obese mice were more pronounced than that observed in lean wild-type mice. 53 Obesity generally increases the production of estrogens, which are associated with early menarche in girls and delayed puberty in boys. 54,55 In the Tucson cohort, CastroRodriguez et al 56 observed the prevalence of asthma to be greater among obese girls with early menarche (before 11 years of age) than among those with later menarche.…”