{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311559/"]},"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=GSE311559"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity","description":"Caspases are cysteine proteases that regulate programmed cell death. While caspase-6, an executioner caspase, is known for its role in neurodegeneration and cell death, its broader physiological functions remain poorly understood. Our previous study revealed that caspase-6 drives liver injury and fibrosis in metabolic dysfunction-associate steatohepatitis. Here, we report that caspase-6 deficiency protects against high fat diet-induced obesity. Both global and adipocyte-specific caspase-6 knockout mice exhibit increased energy expenditure, reduced adiposity and inflammation, and improved glucose metabolism. Mechanistically, caspase-6 directly cleaves peroxisome proliferator-activated receptor gamma (PPARγ) and its cofactor specificity protein 1 (SP1), thereby suppressing adipose triglyceride lipase (ATGL) expression. Caspase-6 deficiency restores ATGL, enhancing lipolysis and elevating fatty acyl esters of hydroxy fatty acids (FAHFAs), which alleviate inflammation and enhance insulin sensitivity. These findings uncover a novel Casp6-PPARγ/SP1-ATGL axis in adipose tissue and establish caspase-6 as a potential therapeutic target for obesity and insulin resistance.","dates":{"publication":"2026/04/22"},"accession":"GSE311559","cross_references":{"GSM":["GSM9327030","GSM9327021","GSM9327032","GSM9327031","GSM9327020","GSM9327019","GSM9327027","GSM9327026","GSM9327029","GSM9327028","GSM9327023","GSM9327034","GSM9327033","GSM9327022","GSM9327036","GSM9327025","GSM9327035","GSM9327024"],"GPL":["30172"],"GSE":["311559"],"taxon":["Mus musculus"],"PMID":["[41969066]"]}}