International Session（Symposium）2(JSH・JSGE・JSGCS)
Thu. November 5th   15:50 - 17:00   Room 5: Portopia Hotel South Wing Ohwada A
IS-S2-2_H
 Changes of hepatocyte autophagy in livers of alcoholic liver disease
Hayato Hikita1, Tomohide Tatsumi1, Tetsuo Takehara1
1Department of Gastroenterology and Hepatology, Osaka University
In nonalcoholic fatty liver disease, we previously reported that autophagy of hepatocytes is suppressed through enhanced Rubicon expression leading to exacerbation of hepatocyte apoptosis and lipid droplet accumulation. However, hepatocyte autophagy in alcoholic liver injury and its impact on pathogenesis has not been studied in detail, and we examined them in the present study.
Ethanol administration into AML12 cells decreased autophagic flux and increased fat accumulation and hepatocyte apoptosis in a concentration-dependent manner. Palmitic acid administration into AML12 cells also decreased autophagic flux and additional ethanol administration further decreased autophagic flux and induced more hepatocyte apoptosis compared to administration of palmitic acid alone. Chronic and binge ethanol feeding to mice enhanced expression levels of LC3-II and P62 in their livers and increased the number of autophagosomes detected by electron microscope in their hepatocytes, which suggests that autophagy was impaired in their livers. It also increased fat accumulation, serum ALT levels and serum caspase 3/7 activity. Ethanol administration did not increase Rubicon expression in AML12 cells or murine livers. Knockdown of Rubicon in AML12 cells or hepatocyte-specific knock out of Rubicon in mice did not ameliorate ethanol-induced autophagy impairment, hepatitis or steatosis.
It is suggested that hepatocyte autophagy is impaired in alcoholic liver disease independent from Rubicon, while it is impaired by Rubicon enhancement in NAFLD.
Index Term 1: apoptosis
Index Term 2: steatosis
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