{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319144/"]},"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=GSE319144"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MARCHF6-ERAD regulates hepatic lipid metabolism and MASLD development","description":"Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a growing global health concern. Increased de novo lipogenesis (DNL), largely mediated by Sterol Regulatory Element-Binding Protein 1 (SREBP1), is a hallmark of MASLD. However, the post-translational mechanisms regulating SREBP1 turnover remain poorly understood. The endoplasmic reticulum-associated degradation (ERAD) pathway ensures protein quality and quantity control, yet its role in hepatic lipid metabolism remains elusive. Here, we investigate the function of the ERAD-specific E3 ubiquitin ligase MARCHF6 in hepatic lipid homeostasis and MASLD pathogenesis.We found hepatic MARCHF6 expression was significantly reduced in both MASLD mouse models and human patients. Liver-specific Marchf6 deletion aggravated hepatic lipid accumulation, fibrosis, and inflammation. Transcriptomic and proteomic analyses revealed upregulation of lipogenic genes in Marchf6Alb livers, with a marked increase in SREBP1 protein levels. Mechanistically, MARCHF6 directly interacted with and ubiquitinated SREBP1, targeting it for proteasomal degradation. Loss of MARCHF6 prolonged SREBP1 half-life, driving excessive DNL.","dates":{"publication":"2026/05/28"},"accession":"GSE319144","cross_references":{"GSM":["GSM9512456","GSM9512459","GSM9512457","GSM9512458"],"GPL":["24247"],"GSE":["319144"],"taxon":["Mus musculus"],"PMID":["[42173365]"]}}