Adenosine monophosphate-activated protein kinase involved in early hepatocarcinogenesis associated with nonalcoholic steatohepatitis in rats

doi:10.3969/j.issn.1006-7795.2016.02.019

Abstract

Abstract: Objective To explore the role of adenosine monophosphate-activated protein kinase(AMPK) in the development of precancerosis induced by a high-fat diet and diethylnitrosamine and its molecular mechanism.Methods The low dose of diethylnitrosamine(DEN, 30mg/kg, ip) and high fat diet(16 weeks)induced liver precancerosis of rat model in vivo was established to observe the pathological changes of rat livers by HE staining.The expression levels of glutathione S-transferase-π(GST-π), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase 1(SCD1), AMPK, p-AMPK were detected by Western blotting, Real-time PCR and immunohistochemistry. The rat cells H4IIE were disposed by palmitic acid(PA) to mimic lipid overload in hepatocarcinoma cells and evaluate the role of AMPK in modulating fat metabolism of hepatocarcinoma.Results We found lipid droplets overload evidently in hepatocytes of rats in DEN+HFD group compared with DEN group, some of which behaving ballooning change, necrosis and inflammatory; meanwhile, GST-π and triglyceride(TG) expression were both elevated significantly in the livers of rats treated with DEN+HFD group when compared with that of DEN group, indicating the precancerosis of rat model induced by NASH was successful.Similarly, the expression of SREBP-1c and its target genes FAS, ACC, SCD1 were all elevated statistically. Furthermore, p-AMPK level was decreased. The in vitro model indicated that TG, SREBP-1c, FAS, ACC, SCD1 were all increased in PA treated cells, while treating cells with AICAR, activator of AMPK, can reverse the effect of PA. Conclusion AMPK is involved in liver precancerosis induced by high-fat diet and diethylnitrosamine, and this process may happen through the inhibition of SREBP-1c.

Key words: diethylnitrosamine, non-alcoholic steatohepatitis, liver precancerosis, adenosine monophosphate-activated protein kinase, sterol regulatory element binding protein-1c

CLC Number:

R575.5

Wang Yunjiao, Han Wenqi, Li Ruofei, Du Zunshu, Wang Xuejiang, Jiang Ying. Adenosine monophosphate-activated protein kinase involved in early hepatocarcinogenesis associated with nonalcoholic steatohepatitis in rats[J]. Journal of Capital Medical University, 2016, 37(2): 208-213.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2016.02.019

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2016/V37/I2/208

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