{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lai P"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["2430"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11897346"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases; however, the relationship between SR-A3 and metabolic dysfunction-associated fatty liver disease (MAFLD) has not been documented. Here, we show that hepatic SR-A3 expression is significantly reduced in human and animal models in the context of MAFLD. Genetic inhibition of SR-A3 in hamsters elicits hyperlipidemia, hyperglycemia, insulin resistance, and hepatic steatosis under chow-diet condition, yet escalates in diet-induced MAFLD. Mechanistically, SR-A3 ablation enhances E3 ligase XIAP-mediated proteasomal ubiquitination of PTEN, leading to AKT hyperactivation. By contrast, hepatic overexpression of human SR-A3 is sufficient to attenuate metabolic disorders in WT hamsters fed a high-fat-high-cholesterol diet "],"journal":["Nature communications"],"pubmed_title":["SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation."],"pmcid":["PMC11897346"],"funding_grant_id":["82070460","8240033347","82270479","HY2021-1"],"pubmed_authors":["Guo X","Mei S","Han Y","Wen S","Miao G","Zhang L","Zhao Y","Dou X","Liu Y","Ding Y","Guo J","Zhao D","Zhang C","Wang Y","Xu L","Shui G","Chen J","Chen G","Xian X","Zhou Z","Zhang W","Li Y","Huang W","Lai P","Lam SM","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation.","description":"Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases; however, the relationship between SR-A3 and metabolic dysfunction-associated fatty liver disease (MAFLD) has not been documented. Here, we show that hepatic SR-A3 expression is significantly reduced in human and animal models in the context of MAFLD. Genetic inhibition of SR-A3 in hamsters elicits hyperlipidemia, hyperglycemia, insulin resistance, and hepatic steatosis under chow-diet condition, yet escalates in diet-induced MAFLD. Mechanistically, SR-A3 ablation enhances E3 ligase XIAP-mediated proteasomal ubiquitination of PTEN, leading to AKT hyperactivation. By contrast, hepatic overexpression of human SR-A3 is sufficient to attenuate metabolic disorders in WT hamsters fed a high-fat-high-cholesterol diet ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-02T20:51:47.299Z","creation":"2025-04-03T23:57:26.627Z"},"accession":"S-EPMC11897346","cross_references":{"pubmed":["40069146"],"doi":["10.1038/s41467-025-57585-0"]}}