Parkin deficiency prevents chronic ethanol-induced hepatic lipid accumulation through β-catenin accumulation

BACKGROUND: Alcohol abuse and alcoholism lead to alcohol liver disease such as alcoholic fatty liver. Parkin is a component of the multiprotein E3 ubiquitin ligase complex and is associated with hepatic lipid accumulation. However, the role of parkin in ethanol-induced liver disease has not been reported. Here, we tested the effect of parkin on ethanol-induced fatty liver in parkin knockout (KO) mice with chronic ethanol feeding. METHODS: Male wild type (WT) and parkin KO mice (10–12 weeks old, n = 10) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. Liver histological, biochemical, and gene-expression studies were performed. RESULTS: Parkin KO mice exhibited lower hepatosteatosis after ethanol consumption. Because several studies reported that β-catenin is a critical factor in ethanol metabolism and protects against alcohol-induced hepatosteatosis, we investigated whether parkin changes β-catenin accumulation in the liver of ethanol-fed mice. Our results show that β-catenin was greatly accumulated in the livers of ethanol-fed parkin KO mice compared to ethanol-fed WT mice, and that parkin binds to β-catenin and promotes its degradation it by ubiquitination. Moreover, the β-catenin inhibitor IWR-1 abrogated the attenuation of ethanol-induced hepatic lipid accumulation by parkin deficiency in the livers of parkin KO mice and parkin siRNA-transfected human hepatic cell line. CONCLUSIONS: Parkin deficiency prevents ethanol-induced hepatic lipid accumulation through promotion of β-catenin signaling by failure of β-catenin degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0424-5) contains supplementary material, which is available to authorized users.