title: Increased pulmonary responses to acute ozone exposure in obese db/db mice.
abstract: Epidemiological studies indicate the incidence of asthma is increased in obese and overweight humans. Responses to ozone (O(3)), 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 O(3) (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than WT mice after air exposure. O(3)-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 O(3) exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O(3) was significantly greater in db/db than WT mice. Previously published results obtained in ob/ob mice were similar except for O(3)-induced neutrophils and MIP-2, which were not different from WT mice. O(3) also induced pulmonary IL-1beta and TNF-alpha 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 O(3). 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 O(3).
authors.affiliation: Physiology Program, Dept. of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115-6021, USA.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Lu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Johnston
authors.forename: Lesley
authors.initials: L
authors.lastname: Flynt
authors.forename: Todd A
authors.initials: TA
authors.lastname: Theman
authors.forename: Raya D
authors.initials: RD
authors.lastname: Terry
authors.forename: Igor N
authors.initials: IN
authors.lastname: Schwartzman
authors.forename: Anna
authors.initials: A
authors.lastname: Lee
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Shore
mesh_terms: D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid; D017931:DNA Primers; D015850:Interleukin-6 / Q000502:physiology; D020738:Leptin / Q000172:deficiency; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D010126:Ozone / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D012143:Respiratory Physiological Phenomena / Q000187:drug effects
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D020738:Leptin; D012313:RNA; D010126:Ozone