title: Effects of leptin deficiency on postnatal lung development in mice.
abstract: Leptin modulates energy metabolism and lung development. We hypothesize that the effects of leptin on postnatal lung development are volume dependent from 2 to 10 wk of age and are independent of hypometabolism associated with leptin deficiency. To test the hypotheses, effects of leptin deficiency on lung maturation were characterized in age groups of C57BL/6J mice with varying Lep(ob) genotypes. Quasi-static pressure-volume curves and respiratory impedance measurements were performed to profile differences in respiratory system mechanics. Morphometric analysis was conducted to estimate alveolar size and number. Oxygen consumption was measured to assess metabolic rate. Lung volume at 40-cmH(2)O airway pressure (V(40)) increased with age in each genotypic group, and V(40) was significantly (P < 0.05) lower in leptin-deficient (ob/ob) mice beginning at 2 wk. Differences were amplified through 7 wk of age relative to wild-type (+/+) mice. Morphometric analysis showed that alveolar surface area was lower in ob/ob compared with +/+ and heterozygote (ob/+) mice beginning at 2 wk. Unlike the other genotypic groups, alveolar size did not increase with age in ob/ob mice. In another experiment, ob/ob at 4 wk received leptin replacement (5 microg.g(-1) x day(-1)) for 8 days, and expression levels of the Col1a1, Col3a1, Col6a3, Mmp2, Tieg1, and Stat1 genes were significantly increased concomitantly with elevated V(40). Leptin-induced increases in V(40) corresponded with enlarged alveolar size and surface area. Gene expression suggested a remodeling event of lung parenchyma after exogenous leptin replacement. These data support the hypothesis that leptin is critical to postnatal lung remodeling, particularly related to increased V(40) and enlarged alveolar surface area.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD 21205, USA.
authors.forename: Kewu
authors.initials: K
authors.lastname: Huang
authors.forename: Richard
authors.initials: R
authors.lastname: Rabold
authors.forename: Eric
authors.initials: E
authors.lastname: Abston
authors.forename: Brian
authors.initials: B
authors.lastname: Schofield
authors.forename: Vikas
authors.initials: V
authors.lastname: Misra
authors.forename: Ewa
authors.initials: E
authors.lastname: Galdzicka
authors.forename: Hannah
authors.initials: H
authors.lastname: Lee
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.forename: Clarke G
authors.initials: CG
authors.lastname: Tankersley
mesh_terms: D000375:Aging / Q000502:physiology; D000399:Air Pressure; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D005260:Female; D020738:Leptin / Q000172:deficiency* / Q000235:genetics*; D008168:Lung / Q000254:growth & development*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D011650:Pulmonary Alveoli / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015656:Respiratory Mechanics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020738:Leptin; D012333:RNA, Messenger