title: 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.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA. sshore@hsph.harvard.edu
authors.forename: S A
authors.initials: SA
authors.lastname: Shore
authors.forename: Y M
authors.initials: YM
authors.lastname: Rivera-Sanchez
authors.forename: I N
authors.initials: IN
authors.lastname: Schwartzman
authors.forename: R A
authors.initials: RA
authors.lastname: Johnston
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001993:Bronchodilator Agents / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D010641:Phenotype; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology
chemical_list: D001993:Bronchodilator Agents; D016207:Cytokines; D020738:Leptin; D010083:Oxidants, Photochemical; D016210:Methacholine Chloride; D010126:Ozone