Role of β-arrestin 1 in the course of non-alcoholic fatty liver disease progressing to hepatocellular carcinoma

Abstract

Objective To investigate the changes and role of β-arrestin 1 in the course of non-alcoholic fatty liver disease (NAFLD) progressing to hepatocellular carcinoma (HCC). Methods Eighty healthy male C57BL/6 mice were randomized into the vegetarian diet group and the high fat diet group according to the random number table with 40 mice in each group. Mice in the vegetarian diet group were fed with vegetarian diet (13% calories in fat) and mice in the high fat diet group were fed with high fat diet (58% calories in fat). Eight mice in each group were decapitated at the end of 9 and 24 weeks. The rest mice in each group were decapitated at the end of 48 weeks. The incidence of HCC of two groups was observed. The expression of protein β-arrestin 1 in the liver tissues of mice was detected by Western blot and the mRNA level was examined using TaqMan real time fluorescence quantitative RT-PCR. The incidence of HCC in two groups was compared using Fisher's exact test, and the protein β-arrestin 1 expression and mRNA level of two groups were compared using t test. Spearman correlation analysis was used to evaluate the relationship between protein β-arrestin 1 expression, mRNA level and the feeding duration of high fat diet in high fat diet group. Results The incidence of HCC in the high fat diet group was 18% (4/22), which was significantly higher than 0 (0/23) in the vegetarian diet group (P=0.034). The expression level of protein β-arrestin 1 in liver tissues of mice in the high fat diet group was 2.4±0.5 in the 9th week, which was significantly higher than 1.5±0.4 in the vegetarian diet group (t=2.779, P<0.05). The β-arrestin 1 mRNA level in liver tissues of mice in the high fat diet group in the 9th, 24th and 48th week were 4.1±0.8, 7.8±2.1 and 12.5±1.2 respectively, which were all significantly higher than 2.6±0.7, 3.6±0.6 and 6.9±1.2 in the vegetarian diet group (t=4.029, 5.522, 9.487; P<0.05) . The protein β-arrestin 1 and mRNA level in HCC tissues of mice in the high fat diet group in the 48th week were 4.6±0.5 and 22.0±3.2, which were significantly higher than 1.6±0.4 and 12.5±1.2 in liver tissues at the same period (t=9.600, 7.837; P<0.05). The protein β-arrestin 1 and mRNA level in high fat diet group were positively correlated with the duration of high fat diet (r=0.949, 0.922; P<0.05). Conclusions It is likely to develop NALFD for the mice fed with high fat diet, and the incidence of HCC is significantly increased. β-arrestin 1 may play a role of accelerating the course of NAFLD progressing to HCC. Key words: Fatty liver; Carcinoma, hepatocellular; β-arrestin; Mice