{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304787/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"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=GSE304787"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Therapeutic targeting of lipidated amino acid deficiency ameliorates MASH via a PPARα/CCL2 axis","description":"Metabolic dysfunction-associated steatohepatitis (MASH), affects nearly one-third of the global population with limited pharmacotherapy approved, underscoring the urgent need for new therapeutic strategies. N-acyl amino acids (NAAs), comprising amino acids linked to long-chain fatty acid acyl groups, are gaining interest, yet their metabolic regulation in MASH remains elusive. Metabolomic profiling in mice and humans with MASH revealed a marked depletion of NAAs, particularly C18:1-Leu, which inversely correlated with disease severity. The bidirectional PM20D1 expression was suppressed in the livers of human and mice with MASH, as well as in lipid-loaded primary mouse hepatocytes and hepatic cell lines. Stable isotope tracing studies in mice with and without MASH confirmed reduced biosynthesis of C18:1-Leu. Genetically, hepatocyte-specific overexpression of PM20D1 or pharmacological treatment with exogenous C18:1-Leu significantly attenuated or reversed established MASH. Mechanistically, C18:1-Leu bound and activated peroxisome proliferator-activated receptor alpha (PPARα), enhancing fatty acid β-oxidation and suppressing the NF-κB/CCL2 axis, thereby reducing hepatic macrophage infiltration, inflammation, and fibrosis. These therapeutic effects were abolished in hepatocyte-specific PPARα- and CCL2-deficient mice, identifying C18:1-Leu as a promising metabolic therapy for MASH.","dates":{"publication":"2026/07/01"},"accession":"GSE304787","cross_references":{"GSM":["GSM9157290","GSM9157291","GSM9157300","GSM9157289","GSM9157301","GSM9157298","GSM9157288","GSM9157299","GSM9157296","GSM9157297","GSM9157294","GSM9157295","GSM9157292","GSM9157293"],"GPL":["15103"],"GSE":["304787"],"taxon":["Mus musculus"]}}