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In this study, we found that primary mouse alveolar epithelial cells (AECs) conducted robust fatty acid oxidation (FAO). More importantly, FAO was strikingly impaired in AECs of mice with LPS-induced ALI. The metabolic deficiency in these cells was likely due to decreased expression of key mediators involved in FAO and mitochondrial bioenergenesis, such as peroxisome proliferator\u2013activated receptor \u03b3 coactivator (PGC)-1\u03b1, carnitine palmitoyltransferase 1A, and medium-chain acyl-CoA dehydrogenase (CAD). We found that treatment of alveolar epithelial line MLE-12 cells with BAL fluids from mice with ALI decreased FAO, and this effect was largely replicated in MLE-12 cells treated with the proinflammatory cytokine TNF-\u03b1, which was consistent with downregulations of PGC-1\u03b1, carnitine palmitoyltransferase 1A, long-chain CAD, and medium-chain CAD in the same treated cells. Furthermore, we found that the BAL fluids from ALI mice and TNF-\u03b1 inhibited MLE-12 bioenergenesis and promoted cell apoptosis. In delineation of the role of FAO in ALI in vivo, we found that conditional ablation of AEC PGC-1\u03b1 aggravated LPS-induced ALI. In contrast, fenofibrate, an activator of the PPAR-\u03b1\/PGC-1\u03b1 cascade, protected mice from this pathology. In summary, these data suggest that FAO is essential to AEC bioenergenesis and functional homeostasis. This study also indicates that FAO impairment\u2013induced AEC dysfunction is an important contributing factor to the pathogenesis of ALI.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0152oc","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T11:41:11Z","timestamp":1536147671000},"page":"167-178","source":"Crossref","is-referenced-by-count":88,"title":["Impairment of Fatty Acid Oxidation in Alveolar Epithelial Cells Mediates Acute Lung Injury"],"prefix":"10.1093","volume":"60","author":[{"given":"Huachun","family":"Cui","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, 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