@article{25c6b0aab5ee4f1da3f39bb89bd99f5f,
title = "Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD",
abstract = "Alveolar epithelial type II (AEC2) cells strictly regulate lipid metabolism to maintain surfactant synthesis. Loss of AEC2 cell function and surfactant production are implicated in the pathogenesis of the smoking-related lung disease chronic obstructive pulmonary disease (COPD). Whether smoking alters lipid synthesis in AEC2 cells and whether altering lipid metabolism in AEC2 cells contributes to COPD development are unclear. In this study, high-throughput lipidomic analysis revealed increased lipid biosynthesis in AEC2 cells isolated from mice chronically exposed to cigarette smoke (CS). Mice with a targeted deletion of the de novo lipogenesis enzyme, fatty acid synthase (FASN), in AEC2 cells (FasniΔAEC2) exposed to CS exhibited higher bronchoalveolar lavage fluid (BALF) neutrophils, higher BALF protein, and more severe airspace enlargement. FasniΔAEC2 mice exposed to CS had lower levels of key surfactant phospholipids but higher levels of BALF ether phospholipids, sphingomyelins, and polyunsaturated fatty acid–containing phospholipids, as well as increased BALF surface tension. FasniΔAEC2 mice exposed to CS also had higher levels of protective ferroptosis markers in the lung. These data suggest that AEC2 cell FASN modulates the response of the lung to smoke by regulating the composition of the surfactant phospholipidome.",
author = "Fan, {Li Chao} and Keith McConn and Maria Plataki and Sarah Kenny and Williams, {Niamh C.} and Kihwan Kim and Quirke, {Jennifer A.} and Yan Chen and Maor Sauler and M{\"o}bius, {Matthias E.} and Chung, {Kuei Pin} and Gomez, {Estela Area} and Choi, {Augustine M.K.} and Xu, {Jin Fu} and Cloonan, {Suzanne M.}",
note = "Funding Information: This work was supported by the National Natural Science Foundation of China (81925001 to JFX and 81800063 to LCF) and by the NIH grant P01 HL114501 (AMKC). SMC is supported by Science Foundation Ireland (Future Research Leaders Grant FRL4862). MP is supported by NIH grant K08 HL157728. The authors thank Clay F. Semenkovich (Washington University) and Brigid L. M. Hogan (Duke University) for sharing the FasnloxP/loxP mice and SftpcCreERT2+/+ mice, respectively. The authors wish to thank Elizabeth Perez, Jong-Seok Moon, Kiichi Nakahira, and Shu Hisata for technical support. The authors also thank Jenny Zhaoying Xiang and Adrian Y. Tan in the Genomic Resources Core Facility of Weill Cornell Medicine for transcriptomic profiling and data analysis as well as Maria Jiao of the Weill Cornell Medicine Laboratory of Comparative Pathology, supported in part by NIH National Cancer Institute grant P30 CA008748. The authors also thank Oliver Yimeng Xu in the Lipidomics Core at Columbia University for lipidomic analysis. Publisher Copyright: Copyright: {\textcopyright} 2023, Fan et al.",
year = "2023",
doi = "10.1172/jci.insight.163403",
language = "English (US)",
volume = "8",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "16",
}