Dataset Information

SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice.

ABSTRACT: Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of cell death-inducing DFF45-like effector (CIDE) protein. The initial function of CIDE is the promotion of cell death and DNA fragmentation in mammalian cells. Cidea was recently reported to play critical roles in the development of hepatic steatosis. The purpose of present study is to determine the effect of chronic alcohol intake on Cidea expression in the livers of mice with alcoholic fatty liver disease. Cidea expression was significantly increased in the liver of alcohol-induced fatty liver mice. While, knockdown of Cidea caused lipid droplets numbers reduction. Next, we detected the activity of ALDH2 reduction and the concentration of serum acetaldehyde accumulation in our alcohol-induced fatty liver mice. Cidea expression was elevated in AML12 cells exposed to 100uM acetaldehyde. Interestingly, Dual-luciferase reporter gene assay showed that 100?uM acetaldehyde led to the activation of Cidea reporter gene plasmid which containing SRE element. What's more, the knockdown of SREBP1c suppressed acetaldehyde-induced Cidea expression. Overall, our findings suggest that Cidea is highly associated with alcoholic fatty liver disease and Cidea expression is specifically induced by acetaldehyde, and this up-regulation is most likely mediated by SREBP1c.

SUBMITTER: He Q

PROVIDER: S-EPMC5775393 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice.

He Qi Q Diao Yan Y Zhao Tingting T Hou Baoyu B Ngokana Linel Darrel LD Liang Huan H Nie Junhui J Tan Peizhu P Huang Hui H Li Yanze Y Qi Lin L Zhao Yuanyuan Y Liu Ying Y Gao Xu X Zhou Lingyun L

Scientific reports 20180119 1

Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of cell death-inducing DFF45-like effector (CIDE) protein. The initial function of CIDE is the promotion of cell death and DNA fragmentation in mammalian cells. Cidea was recently reported to play critical roles in the development of hepatic steatosis. The purpose of present study is to determine the effect of chronic alcohol intake on Cidea expression in the livers of mice with alcoholic fatty liver disease. Cidea exp ...[more]

PMID: 29352167

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Project description:Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease of life, usually caused by unhealthy diet and lifestyle. Compared to normal individuals, the structure of the intestinal flora of NAFLD patients is altered accordingly. This study investigates the effect of camel milk on the regulation of intestinal flora structure in mice with high-fat diet-induced NAFLD. NAFLD model was established by feeding C57BL/6J mice a high-fat diet for 12 weeks, meanwhile camel milk (3.0 g/kg/d), cow milk (3.0 g/kg/d), and silymarin (200 mg/kg/d) were administered by gavage, respectively. Food intake and changes of physiological indexes in mice were observed and recorded. The 16S rRNA gene V3-V4 region was sequenced and the intestinal flora diversity and gene function were predicted in the colon contents of mice from different group. The results showed that camel milk enhanced glucolipid metabolism by downregulate the levels of blood glucose and triglyceride (TG) in serum, reduced lipid accumulation by downregulate the level of TG in the liver and improved liver tissue structure in NAFLD mice (p < 0.05). Meanwhile, camel milk had a positive modulatory effect on the intestinal flora of NAFLD mice, increasing the relative abundance of beneficial bacteria and decreasing the relative abundance of harmful bacteria in the intestinal flora of NAFLD mice, and silymarin had a similar modulatory effect. At the genus level, camel milk increased the relative abundance of Bacteroides, norank_f_Muribaculaceae and Alloprevotella and decreased the relative abundance of Dubosiella and Coriobacteriaceae_UCG-002 (p < 0.05). Camel milk also enhanced Carbohydrate metabolism, Amino acid metabolism, Energy metabolism, Metabolism of cofactors and vitamins and Lipid metabolism in NAFLD mice, thus reducing the degree of hepatic lipid accumulation in NAFLD mice and maintaining the normal structure of the liver. In conclusion, camel milk can improve the structure and diversity of intestinal flora and enhance the levels of substance and energy metabolism in NAFLD mice, which has a positive effect on alleviating NAFLD and improving the structure of intestinal flora.

Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma (HCC). However, the mechanistic pathways that link both disorders are essentially unknown.ObjectiveOur study was designed to investigate the role of microRNA-21 in the pathogenesis of NAFLD and its potential involvement in HCC.MethodsWildtype mice maintained on a high fat diet (HFD) received tail vein injections of microRNA-21-anti-sense oligonucleotide (ASO) or miR-21 mismatched ASO for 4 or 8 weeks. Livers were collected after that time period for lipid content and gene expression analysis. Human hepatoma HepG2 cells incubated with oleate were used to study the role of miR-21 in lipogenesis and analysed with Nile-Red staining. microRNA-21 function in carcinogenesis was determined by soft-agar colony formation, cell cycle analysis and xenograft tumour assay using HepG2 cells.ResultsThe expression of microRNA-21 was increased in the livers of HFD-treated mice and human HepG2 cells incubated with fatty acid. MicroRNA-21 knockdown in those mice and HepG2 cells impaired lipid accumulation and growth of xenograft tumour. Further studies revealed that Hbp1 was a novel target of microRNA-21 and a transcriptional activator of p53. It is well established that p53 is a tumour suppressor and an inhibitor of lipogenesis by inhibiting Srebp1c. As expected, microRNA-21 knockdown led to increased HBP1 and p53 and subsequently reduced lipogenesis and delayed G1/S transition, and the additional treatment of HBP1-siRNA antagonised the effect of microRNA-21-ASO, suggesting that HBP1 mediated the inhibitory effects of microRNA-21-ASO on both hepatic lipid accumulation and hepatocarcinogenesis. Mechanistically, microRNA-21 knockdown induced p53 transcription, which subsequently reduced expression of genes controlling lipogenesis and cell cycle transition. In contrast, the opposite result was observed with overexpression of microRNA-21, which prevented p53 transcription.ConclusionsOur findings reveal a novel mechanism by which microRNA-21, in part, promotes hepatic lipid accumulation and cancer progression by interacting with the Hbp1-p53-Srebp1c pathway and suggest the potential therapeutic value of microRNA-21-ASO for both disorders.

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SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice.

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SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic fatty liver Mice.

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