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Analysis of piRNA expression spectra in a non-alcoholic fatty liver disease mouse model induced by a methionine- and choline-deficient diet.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) has become a common health issue worldwide, and P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) have been shown to be differentially expressed in a variety of diseases. The aim of the present study was to investigate the potential relationship between piRNA and NAFLD. A NAFLD mouse model was established using a methionine- and choline-deficient (MCD) diet and methionine- and choline-sufficient (MCS) diet. Following this, mouse liver tissues were removed and stained with hematoxylin and eosin, and the levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol and triglyceride were measured. Moreover, the liver tissues of the control and model groups were selected for piRNA gene chip analysis to identify piRNAs with differential expression in NAFLD. In addition, the differentially expressed piRNAs screened from the microarray were assessed by reverse transcription-quantitative PCR (RT-qPCR). piRNAs with potential research value were also selected for further analysis of target genes, using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The present study identified a total of 1,285 piRNAs with differential expression levels. The results indicated that in the model group, 641 piRNAs were upregulated, while 644 piRNAs were downregulated. Furthermore, piRNAs were enriched in 'cancer', 'Hippo signaling', 'Wnt signaling' and 'Mitogen-activated protein kinase signaling' pathways. The RT-qPCR results demonstrated that piRNA DQ566704 and piRNA DQ723301 were significantly upregulated in the model group, which was largely consistent with the analysis results of the piRNA arrays. Therefore, the results of the piRNA arrays and the further analyses in the present study were considered reliable. Collectively, the present results suggest that differentially expressed piRNAs exist in NAFLD and may affect the development of NAFLD via related pathways.

SUBMITTER: Ma X

PROVIDER: S-EPMC7185076 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Analysis of piRNA expression spectra in a non-alcoholic fatty liver disease mouse model induced by a methionine- and choline-deficient diet.

Ma Xuyang X Huang Yumei Y Ding Ying Y Shi Lei L Zhong Xiaoling X Kang Ming M Li Changping C

Experimental and therapeutic medicine 20200409 6

Non-alcoholic fatty liver disease (NAFLD) has become a common health issue worldwide, and P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) have been shown to be differentially expressed in a variety of diseases. The aim of the present study was to investigate the potential relationship between piRNA and NAFLD. A NAFLD mouse model was established using a methionine- and choline-deficient (MCD) diet and methionine- and choline-sufficient (MCS) diet. Following this, mouse liver tissu ...[more]

PMID: 32346447

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Project description:BackgroundEmerging data support a role for lipids in non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in humans. With experimental models such data can be challenged or validated. Mice fed a low-methionine, choline-deficient (LMCD) diet develop NASH and, when injected with diethylnitrosamine (DEN), HCC. Here, lipidomic analysis was used to elucidate whether the NASH and HCC associated lipid derangements resemble the lipid profile of the human disease.MethodsLipids were measured in the liver of mice fed a control or a LMCD diet for 16 weeks. DEN was injected at young age to initiate hepatocarcinogenesis. DEN treatment associated changes of the lipid composition and the tumor lipidome were evaluated.ResultsLMCD diet fed mice accumulated ceramides and triacylglycerols in the liver. Phospholipids enriched with monounsaturated fatty acids were also increased, whereas hepatic cholesterol levels remained unchanged in the LMCD model. Phosphatidylcholine and lysophosphatidylcholine concentrations declined in the liver of LMCD diet fed mice. The changes of most lipids associated with LMCD diet feeding were similar between water and DEN injected mice. Several polyunsaturated (PU) diacylglycerol species were already low in the liver of DEN injected mice fed the control diet. Tumors developed in the liver of LMCD diet fed mice injected with DEN. The tumor specific lipid profile, however, did not resemble the decrease of ceramides and PU phospholipids, which was consistently described in human HCC. Triacylglycerols declined in the cancer tissues, which is in accordance with a low expression of lipogenic enzymes in the tumors.ConclusionsThe LMCD model is suitable to study NASH associated lipid reprogramming. Hepatic lipid profile was modestly modified in the DEN injected mice suggesting a function of these derangements in carcinogenesis. Lipid composition of liver tumors did not resemble the human HCC lipidome, and most notably, lipogenesis and triacylglycerol levels were suppressed.

Dataset Information

Analysis of piRNA expression spectra in a non-alcoholic fatty liver disease mouse model induced by a methionine- and choline-deficient diet.

Publications

Analysis of piRNA expression spectra in a non-alcoholic fatty liver disease mouse model induced by a methionine- and choline-deficient diet.

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