IDDF2018-ABS-0210 Pokemon over-expression accelerates the progression of NAFLD via increasing lipid droplet deposit in hepatocyte

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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome and is characterised by the accumulation of lipid droplets. Pokemon (FBI-1/ZATB7A) is an important proto-oncogene which is involved in cancer development and adipogenic gene expression. The aim of our study is to explore the role of Pokemon in the development and progression of NAFLD.

Methods

C57BL/6 mice were fed with normal chow (NC) or high-fat diet (HFD) for 16 weeks to induce NAFLD. Pokemon mRNA and protein were detected by RT-PCR and Western-blot as well as immunohistochemistry. NAFLD cell models were established by oleic acid, and si-Pokemon hepatic cancer cell lines were also constructed by plko lentiviral system.

Results

Mice fed with HFD for 16 weeks showed increased body weight, liver weight, liver-to-body weight ratio as well as increased lipid accumulation as shown by H and E staining and Oil Red O staining consistent with the establishment of NAFLD. The Pokemon mRNA as determined by RT-PCR and protein expression as determined by Western blot and immunohistochemistry were significantly increased in mice fed with HFD compared with the NC group(p<0.01). The upregulated Pokemon was accompanied by increased serum TNF-α, IL-6, triglyceride, cholesterol and MDA levels in HFD group (p<0.01). For in vitro study, Pokemon and SREBP-1 protein expression in HepG2 were increased in a concentration-dependent manner when treated with oleic acid (p<0.01). SREBP-1 and FAS mRNA expression were also increased which could be counteracted by pokemon silencing. Knockdown pokemon by si RNA in HepG2 cells showed decreased lipid accumulation, triglyceride content, suppressed mRNA expression of lipogenic genes including FASN, SREBP, SCD-1, HMGCR and genes related with oxidation metabolism including Cpt1 and Acadm.

Conclusions

Pokemon promotes NAFLD progression via increasing lipid accumulation and repressing free acids oxidation.

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