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Increased pulmonary responses to acute ozone exposure in obese db/db mice

¹Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; and ²Department of Pediatrics, National Taiwan University Hospital and Medical College, National Taiwan University, Taipei, Taiwan

Submitted 9 September 2005 ; accepted in final form 14 December 2005

Epidemiological studies indicate the incidence of asthma is increased in obese and overweight humans. Responses to ozone (O₃), an asthma trigger, are increased in obese (ob/ob) mice lacking the satiety hormone leptin. The long form of leptin receptor (Ob-R_b) is required for satiety; mice lacking this receptor (db/db mice) are also substantially obese. Here, wild-type (WT) and db/db mice were exposed to air or O₃ (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than WT mice after air exposure. O₃-induced increases in pulmonary resistance and airway responsiveness were also greater in db/db mice. BALF eotaxin, IL-6, KC, and MIP-2 increased 4 h after O₃ exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O₃ was significantly greater in db/db than WT mice. Previously published results obtained in ob/ob mice were similar except for O₃-induced neutrophils and MIP-2, which were not different from WT mice. O₃ also induced pulmonary IL-1 and TNF- mRNA expression in db/db but not ob/ob mice. Leptin was increased in serum of db/db mice, and pulmonary mRNA expression of short form of leptin receptor (Ob-R_a) was similar in db/db and WT mice. These data confirm obese mice have innate airway hyperresponsiveness and increased pulmonary responses to O₃. Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-R_b but not Ob-R_a, suggest leptin, acting through Ob-R_a, can modify some pulmonary responses to O₃.

leptin; interleukin-1; airway responsiveness; macrophage inflammatory protein-2; neutrophil; ventilation

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