Obstructive Sleep Apnea Syndrome Exacerbates NASH Progression via Selective Autophagy‐Mediated Eepd1 Degradation

• DOI: 10.1002/advs.202405955
• Publication Date: 2024-06-26T05:39:45Z
• Authors: Jie Xiong; Ying Xu; Ning Wang; Shengming Wang; Yao Zhang; Sijia Lu; Xiaoman Zhang; Xingxing Liang; Chuchu Liu; Quanxin Jiang; Junting Xu; Qiqi Qian; Peihui Zhou; Limin Yin; Feng Liu; Suzhen Chen; Shankai Yin; Junli Liu
• Keywords: Steatohepatitis; Knockout mouse; Steatosis

Obstructive sleep apnea syndrome (OSAS), characterized by chronic intermittent hypoxia (CIH), is an independent risk factor for aggravating non-alcoholic steatohepatitis (NASH). The prevailing mouse model employed in CIH research inadequate the comprehensive exploration of impact on NASH development due to reduced food intake observed CIH-exposed mice, which deviates from human responses. To address this issue, a pair-feeding investigation with and normoxia-exposed mice conducted. It revealed that exposure aggravates DNA damage, leading hepatic fibrosis inflammation. analysis genome-wide association study (GWAS) data also discloses between Eepd1, repair enzyme, OSAS. Furthermore, it triggered selective autophagy, autophagic degradation thereby exacerbating damage hepatocytes. Notably, Eepd1 liver-specific knockout exhibit aggravated further progression NASH. identify therapeutic approach CIH-induced NASH, drug screening conducted found Retigabine dihydrochloride suppresses CIH-mediated degradation, alleviated These findings imply targeting can be adjunctive treatment exacerbated