{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300375/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300375"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Dietary lipid stress aggravates obstructive lung injury involving epithelial IGF-1-Akt dysfunction and epithelial-endothelial crosstalk","description":"Metabolic comorbidities are common in chronic obstructive pulmonary disease (COPD), but how systemic lipid excess affects lungs with established obstructive pathology remains unclear. We integrated a βENaC-transgenic muco-obstructive lung disease model, an elastase-induced emphysema model, whole-lung transcriptomics, epithelial and endothelial cell systems, and a health-screening cohort. A high-fat diet (HFD) increased body weight, glycemia, and adiposity in both wild-type and βENaC-transgenic mice, but further enlarged distal airspaces and reduced FEV0.1/FVC in βENaC-transgenic mice. Transcriptomic and tissue analyses revealed remodeling of lipid-handling, PI3K-Akt, and vascular programs, accompanied by reduced Akt phosphorylation, increased FOXO1 abundance and Fasl expression, and increased TUNEL positivity in epithelial regions. Palmitate attenuated IGF-1-induced Akt activation in bronchial epithelial cells, whereas IGF-1 receptor inhibition reproduced Akt suppression and apoptosis-related responses without recapitulating the full HFD phenotype. HFD preconditioning also increased subsequent elastase-induced airspace enlargement. Palmitate directly induced endothelial inflammatory and junction-associated responses, while conditioned medium from palmitate-exposed ENaC-hyperactive epithelial cells enhanced endothelial IL6 and VCAM1 expression. Hepatic steatosis coincided with lower percent-predicted FEV1 in men with airflow obstruction. These findings support a multicompartment model in which systemic lipid stress compromises epithelial survival signaling and vascular homeostasis in obstructive lung disease.","dates":{"publication":"2026/09/08"},"accession":"GSE300375","cross_references":{"GSM":["GSM9059279","GSM9059269","GSM9059280","GSM9059270","GSM9059273","GSM9059274","GSM9059271","GSM9059272","GSM9059277","GSM9059278","GSM9059275","GSM9059276"],"GPL":["24247"],"GSE":["300375"],"taxon":["Mus musculus"]}}