Alveolar-capillary adaptation to chronic hypoxia in the fatty lung

C. Yilmaz, P. Ravikumar, D. Gyawali, R. Iyer, R. H. Unger, C. C W Hsia

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Obese diabetic (ZDF fa/fa) rats with genetic leptin resistance suffer chronic lipotoxicity associated with age-related lung restriction and abnormal alveolar ultrastructure. We hypothesized that these abnormalities impair adaptation to ambient hypoxia. Methods: Male fa/fa and lean (+/+) ZDF rats (4-months old) were exposed to 21 or 13% O2 for 3 weeks. Lung function was measured under anaesthesia. Lung tissue was assayed for DNA damage and ultrastructure measured by morphometry. Results: In normoxia, lung volume, compliance and diffusing capacity were lower, while blood flow was higher in fa/fa than +/+ rats. In hypoxia, fa/fa animals lost more weight, circulating hematocrit rose higher, and lung volume failed to increase compared to +/+. In fa/fa, the hypoxia-induced increase in post-mortem lung volume was attenuated (19%) vs. +/+ (39%). Alveolar ducts were 35% smaller in normoxia but enlarged twofold more in hypoxia compared to +/+. Hypoxia induced broad increases (90-100%) in the volumes and surface areas of alveolar septal components in +/+ lungs; these increases were moderately attenuated in fa/fa lungs (58-75%), especially that of type II epithelium volume (16 vs. 61% in +/+). In fa/fa compared to +/+ lungs, oxidative DNA damage was greater with increased hypoxia induced efflux of alveolar macrophages. Harmonic mean thickness of the diffusion barrier was higher, indicating higher structural resistance to gas transfer. Conclusion: Chronic lipotoxicity impaired hypoxia-induced lung expansion and compensatory alveolar growth with disproportionate effect on resident alveolar progenitor cells. The moderate structural impairment was offset by physiological adaptation primarily via a higher hematocrit.

Original languageEnglish (US)
Pages (from-to)933-946
Number of pages14
JournalActa Physiologica
Issue number4
StatePublished - Apr 1 2015


  • High-altitude adaptation
  • Lipotoxicity
  • Lung function
  • Lung morphometry
  • Metabolic syndrome
  • Obesity

ASJC Scopus subject areas

  • Physiology


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