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The prevailing mouse model employed in CIH research is inadequate for the comprehensive exploration of the impact of CIH on NASH development due to reduced food intake observed in CIH\u2010exposed mice, which deviates from human responses. To address this issue, a pair\u2010feeding investigation with CIH\u2010exposed and normoxia\u2010exposed mice is conducted. It is revealed that CIH exposure aggravates DNA damage, leading to hepatic fibrosis and inflammation. The analysis of genome\u2010wide association study (GWAS) data also discloses the association between Eepd1, a DNA repair enzyme, and OSAS. Furthermore, it is revealed that CIH triggered selective autophagy, leading to the autophagic degradation of Eepd1, thereby exacerbating DNA damage in hepatocytes. Notably, <jats:italic>Eepd1<\/jats:italic> liver\u2010specific knockout mice exhibit aggravated hepatic DNA damage and further progression of NASH. To identify a therapeutic approach for CIH\u2010induced NASH, a drug screening is conducted and it is found that Retigabine dihydrochloride suppresses CIH\u2010mediated Eepd1 degradation, leading to alleviated DNA damage in hepatocytes. These findings imply that targeting CIH\u2010mediated Eepd1 degradation can be an adjunctive approach in the treatment of NASH exacerbated by OSAS.<\/jats:p>","DOI":"10.1002\/advs.202405955","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T01:39:45Z","timestamp":1719365985000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Obstructive Sleep Apnea Syndrome Exacerbates NASH Progression via Selective Autophagy\u2010Mediated Eepd1 Degradation"],"prefix":"10.1002","volume":"11","author":[{"given":"Jie","family":"Xiong","sequence":"first","affiliation":[{"name":"Shanghai Diabetes Institute Department of Endocrinology and Metabolism Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 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