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However, high oxygen doses may cause hyperoxic acute lung injury (HALI). In line with the obesity pandemic, numbers of ARDS patients with obesity are rising. Epidemiological data suggest higher morbidity but lower mortality in obese ARDS patients. However, it is currently unclear whether there is a biological basis for this \u201cobesity paradox\u201d. This study used a controlled animal model to investigate influences of diet-induced obesity on HALI-associated structural, molecular and functional changes of the lung.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6N mice were fed either control diet (CD) or high fat diet (HFD) for 30 weeks. A subset of the animals was additionally exposed to normobaric hyperoxia (FiO\n                      <jats:sub>2<\/jats:sub>\n                      : 90%; Hyper) for 72\u00a0h.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hyperoxia was associated with reduced blood oxygenation and mechanical alterations indicative of pulmonary stiffening. Body fat depots were depleted in CD-Hyper, but not in HFD-Hyper groups. Morphological hallmarks of HALI including fragmentation and loss of epithelial cells as well as septal edema were significantly alleviated in hyperoxic obese mice. Diet-group specific changes in protein abundances suggested regulation of cellular stress response in CD-Hyper, whereas in HFD-Hyper predominantly metabolic and cell adaptive processes were altered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Diet-induced obesity did not influence functional measures in the acute phase of hyperoxia but prevented depletion of body fat reserves and mitigated structural lung damage indicating a beneficial impact on regeneration. This supports a biological basis for an obesity paradox in ARDS, and should be taken into account for future individualized prevention and therapy in obese patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-026-03663-w","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:16:30Z","timestamp":1775726190000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diet-induced obesity alleviates epithelial damage in hyperoxic acute lung injury (HALI) in mice"],"prefix":"10.1186","volume":"27","author":[{"given":"Morten","family":"Kampelmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"M\u00fchlfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schipke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"issue":"10358","key":"3663_CR1","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/S0140-6736(22)01485-4","volume":"400","author":"LDJ Bos","year":"2022","unstructured":"Bos LDJ, Ware LB. 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