FRANK LEIGH LUJohnston R.A.Flynt L.Theman T.A.Terry R.D.Schwartzman I.N.Lee A.Shore S.A.2020-12-082020-12-0820061040-0605https://www.scopus.com/inward/record.uri?eid=2-s2.0-33646589670&doi=10.1152%2fajplung.00386.2005&partnerID=40&md5=c75852627aa53e8b651113e8aad1e40dhttps://scholars.lib.ntu.edu.tw/handle/123456789/524951Epidemiological 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-Rb) 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-1β and TNF-α 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-Ra) 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-Rb but not Ob-R a, suggest leptin, acting through Ob-Ra, can modify some pulmonary responses to O3. Copyright ? 2006 the American Physiological Society.Airway responsiveness; Interleukin-1β; Leptin; Macrophage inflammatory protein-2; Neutrophil; Ventilation[SDGs]SDG3eotaxin; interleukin 1beta; interleukin 6; leptin; leptin receptor; macrophage inflammatory protein 2; messenger RNA; ozone; tumor necrosis factor alpha; airway pressure; animal experiment; animal tissue; article; controlled study; female; lung function; lung resistance; mouse; neutrophil; nonhuman; obesity; oscillation; priority journal; protein expression; wild type; Animals; Base Sequence; Bronchoalveolar Lavage Fluid; DNA Primers; Interleukin-6; Leptin; Lung; Mice; Mice, Mutant Strains; Neutrophils; Obesity; Ozone; Polymerase Chain Reaction; Respiratory Physiology; RNAjournal article10.1152/ajplung.00386.2005163736702-s2.0-33646589670