Abstract

The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. In this study, we investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. Forty zebrafish were fed a high-cholesterol diet (1.5 g per day) for 8 weeks. We measured fatty liver changes in the zebrafish liver using oil red O staining and divided them into two groups based on high and low scores. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. Human homologs of lncRNAs were identified using ZFLNC, Ensembl, and NONCODE. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. In particular, eight conserved human homologs of lncRNAs were found. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered.

Highlights

  • The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed

  • Very few long noncoding RNAs (lncRNAs) exhibit sequence conservation across ­species[14,15], since lncRNAs contribute more to cell-line specificity than protein-coding genes proven by Djebali et al.[16], meaningful research on lncRNAs associated with NAFLD is possible if one can find lncRNAs in certain animals that are homologous in humans

  • We found eight human homologs of lncRNA candidates that might be associated with liver metabolism and NAFLD

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Summary

Introduction

The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. We investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered. To identify lncRNAs in the NAFLD zebrafish model, we performed high-cholesterol diet feeding, measured and grouped NAFLD in the liver of zebrafish, and performed next-generation sequencing in the zebrafish liver (Fig. 1).

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