Effects of leptin deficiency on postnatal lung development in mice

Kewu Huang, Richard Rabold, Eric Abston, Brian Schofield, Vikas Misra, Ewa Galdzicka, Hannah Lee, Shyam Biswal, Wayne Mitzner, Clarke G. Tankersley

Research output: Contribution to journalArticle

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 Lepob 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-cmH2O airway pressure (V40) increased with age in each genotypic group, and V40 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 μg·g -1·day-1) for 8 days, and expression levels of the Col1a1, Col3a1, Col6a3, Mmp2, Tieg1, and Stat1 genes were significantly increased concomitantly with elevated V40. Leptin-induced increases in V40 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 V40 and enlarged alveolar surface area.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalJournal of applied physiology
Volume105
Issue number1
DOIs
StatePublished - Jul 2008

Keywords

  • Gene expression profiles
  • Leptin replacement
  • Lung morphometry
  • Metabolic rate
  • Respiratory system mechanics

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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  • Cite this

    Huang, K., Rabold, R., Abston, E., Schofield, B., Misra, V., Galdzicka, E., Lee, H., Biswal, S., Mitzner, W., & Tankersley, C. G. (2008). Effects of leptin deficiency on postnatal lung development in mice. Journal of applied physiology, 105(1), 249-259. https://doi.org/10.1152/japplphysiol.00052.2007