{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE346nnn/GSE346664/"]},"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=GSE346664"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"FSP1 reprograms hepatic lipid metabolism via SIRT1-mediated KU70 deacetylation: an LDLR-bypass atheroprotection","description":"FSP1 (ferroptosis suppressor protein 1) is best known as a guardian against lipid peroxidation, yet whether it governs hepatic lipid homeostasis beyond ferroptosis remains unknown. Here we reported that hepatic FSP1 activates SIRT1, driving KU70 deacetylation that creates a YAP-trapping complex-a previously unrecognized molecular switch. This switch sequesters YAP from TEAD4 and silences ANGPTL3 and confers atheroprotection-without touching LDLR. Furthermore, AAV8-mediated hepatocyte-specific human FSP1 overexpression robustly lowered plasma lipid levels and conferred a protective effect against atherosclerosis in LDLR−/− mice. Notably, analysis of liver data from patients with dyslipidaemia revealed an inverse FSP1-ANGPTL3 correlation. Therefore, our findings redefined FSP1 as a lipid metabolic regulator and uncover a druggable Sirt1-Ku70-YAP cascade for LDLR-bypass lipid lowering.","dates":{"publication":"2026/09/16"},"accession":"GSE346664","cross_references":{"GSM":["GSM10037990","GSM10037991","GSM10037992","GSM10037993","GSM10037994","GSM10037989"],"GPL":["37500"],"GSE":["346664"],"taxon":["Mus musculus"]}}