{"database":"GEO","file_versions":[],"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=GSE332974"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Non-enzymatic hepatic ABHD6 interacts with Akt-FoxO1 axis to regulate metabolic health","description":"The enzymatic function of ABHD6 on insulin secretion and insulin resistance is well documented. However, its non-enzymatic function, especially its effects on metabolic health, including selective hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) is completely unexplored. To define the role of ABHD6 in liver physiology, we generated liver-specific ABHD6 knockout mice, as well as liver-specific overexpression of native and enzymatic inactive mutant ABHD6 mouse models. We demonstrated that non-enzymatic ABHD6 is an unidentified regulator of selective hepatic insulin resistance and contributes to MASLD progression. Mechanistically, we found that ABHD6 located in the nucleus and interacted with Akt/FoxO1 axis to regulate insulin signaling. Our study reveals an entirely different mechanism underlying selective hepatic insulin resistance that involves a previously unknown non-enzymatic function of ABHD6. This study opens an avenue for the development of a novel class of ABHD6 inhibitors to improve metabolic health.","dates":{"publication":"2026/05/26"},"accession":"GSE332974","cross_references":{"GSM":["GSM9756349","GSM9756350","GSM9756351","GSM9756343","GSM9756344","GSM9756352","GSM9756353","GSM9756342","GSM9756347","GSM9756348","GSM9756345","GSM9756346"],"GPL":["34290"],"GSE":["332974"],"taxon":["Mus musculus"]}}