Pulmonary responses to acute ozone exposure in fasted mice: effect of leptin administration.
Leptin is a satiety hormone that also has proinflammatory effects, including augmentation of ozone-induced pulmonary inflammation. The purpose of this study was to determine whether reductions in endogenous levels of leptin can attenuate pulmonary responses to ozone. To reduce serum leptin, we fasted mice overnight before ozone exposure. Fasting caused a marked reduction in serum leptin to approximately one-sixth the levels observed in fed mice, and continuous infusion of leptin via Alzet micro-osmotic pumps restored serum leptin to, but not above, fed levels. Ozone exposure (2 ppm for 3 h) caused a significant, approximately 40% increase in pulmonary resistance (P < 0.01) and increased airway responsiveness in fasted but not in fed mice. The increased effect of ozone on pulmonary mechanics and airway responsiveness in fasted mice was not observed when leptin was restored via continuous infusion. Ozone exposure caused pulmonary inflammation, as evident by increases in bronchoalveolar lavage cells, protein, and soluble tumor necrosis factor receptors. There was no effect of fasting status on ozone-induced changes in the bronchoalveolar lavage inflammatory profile, and leptin treatment did not alter these responses. Our results indicate that fasting augments ozone-induced changes in pulmonary mechanics and airway responsiveness in mice. These effects of fasting are the result of declines in serum leptin. The mechanistic basis for this protective effect of leptin in fasted mice remains to be determined but is not related to effects on ozone-induced inflammation.
Johnston
Richard A
RA
Physiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115-6021, USA.
Theman
Todd A
TA
Terry
Raya D
RD
Williams
Erin S
ES
Shore
Stephanie A
SA
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D015992:Body Mass Index; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D005215:Fasting / Q000502:physiology*; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010126:Ozone / Q000009:adverse effects / Q000494:pharmacology*; D011014:Pneumonia / Q000209:etiology / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology
D020738:Leptin; D010083:Oxidants, Photochemical; D010126:Ozone; D003345:Corticosterone