Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis

• DOI: 10.1016/j.apsb.2023.03.008
• Publication Date: 2023-03-10T07:42:38Z
• Authors: Qian Yu; Chang Li; Qinghui Niu; Jigang Wang; Zhaodi Che; Ke Lei; He Ren; Boyi Ma; Yixing Ren; Pingping Luo; Zhuming Fan; Huan Zhang; Zhaohui Liu; George L. Tipoe; Jia Xiao
• Keywords: Steatohepatitis; Nonalcoholic steatohepatitis; Autophagosome; Pathogenesis

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) autophagy and pathogenesis diet-induced mice. Human fatty liver disease (NAFLD) samples were used examine protein expression COX1 level autophagy. Cox1Δhepa mice their wildtype littermates generated fed with 3 different NASH models. found that was increased patients models accompanied by impaired required for basal hepatocytes specific deletion exacerbated inhibiting Mechanistically, directly interacted WD repeat domain, phosphoinositide interacting 2 (WIPI2), which crucial autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue WIPI2 reversed flux improved phenotypes mice, indicating deletion-mediated partially dependent on WIPI2-mediated In conclusion, we demonstrated a novel role protected against WIPI2. Targeting COX1-WIPI2 axis may be therapeutic strategy NASH.