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We hypothesized that these abnormalities impair adaptation to ambient hypoxia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male fa\/fa and lean (+\/+) <jats:styled-content style=\"fixed-case\">ZDF<\/jats:styled-content> rats (4\u2010months old) were exposed to 21 or 13% O<jats:sub>2<\/jats:sub> for 3\u00a0weeks. Lung function was measured under anaesthesia. Lung tissue was assayed for <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> damage and ultrastructure measured by morphometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010induced increase in post\u2010mortem 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\u2013100%) in the volumes and surface areas of alveolar septal components in +\/+ lungs; these increases were moderately attenuated in fa\/fa lungs (58\u201375%), especially that of type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> epithelium volume (16 vs. 61% in +\/+). In fa\/fa compared to +\/+ lungs, oxidative <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Chronic lipotoxicity impaired hypoxia\u2010induced 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12419","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T13:35:03Z","timestamp":1414848903000},"page":"933-946","source":"Crossref","is-referenced-by-count":11,"title":["Alveolar\u2013capillary adaptation to chronic hypoxia in the fatty lung"],"prefix":"10.1111","volume":"213","author":[{"given":"C.","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Gyawali","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Iyer","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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