Fish Oil Feeding Modulates the Expression of Hepatic MicroRNAs in a Western-Style Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model.

Hualin Wang,Chaodong Wu,Zhiguo Liu,Fahu Yuan,Yang Shao,Na Li,Han Feng,Hongyu Zhang

doi:10.1155/2017/2503847

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide. Recent studies have indicated that fish oil supplementation has benefits against NAFLD. Our previous transcriptomic study has validated the effect of fish oil supplementation on altering hepatic gene expression in a NAFLD rat model. In the current study, we examined the effects of fish oil on the expression of hepatic microRNAs. Male Sprague–Dawley rats were fed with a lab chow (CON), high-fat high-cholesterol diet (WD), or WD supplemented with fish oil (FOH), respectively. Small RNAs were extracted from livers for RNA-sequencing. A total of 79 miRNAs were identified as differentially expressed miRNAs (DEMs) between FOH and WD groups, exemplified by rno-miR-29c-3p, rno-miR-30d-5p, rno-miR-33-5p, rno-miR-34a, and rno-miR-328a-3p. Functional annotation of DEMs predicted target genes suggested that the altered hepatic miRNAs contributed to fish oil modification of hepatic lipid metabolism and signaling transduction. Integrative analysis of DEMs and differentially expressed genes suggested that the expression difference of Pcsk9, Insig2, Per3, and Socs1/3 between FOH and WD groups may be due to miRNA modification. Our study reveals that fish oil supplementation alters hepatic expression of miRNAs, which may contribute to fish oil amelioration of NAFLD in rats.

Highlights

Over the past four decades, overweight and obesity have been implicated as a severe public health problem worldwide
We have illustrated that 16 weeks of fish oil feeding ameliorated WD diet-induced hyperlipidemia, hepatic steatosis, and inflammation, and the transcriptomic study has identified the differentially expressed hepatic mRNAs between the rats fed with WD diet or WD supplemented with fish oil (FOH) [20]
We extracted the small RNAs from livers of six rats in WD or FOH groups, respectively, and constructed the pooled small RNA libraries separately for WD and FOH to identify the differentially expressed miRNAs (DEMs)

Summary

Introduction

Over the past four decades, overweight and obesity have been implicated as a severe public health problem worldwide. Obesity-associated insulin resistance and hyperinsulinemia result in increased hepatic de novo lipogenesis [3, 4]. When having inefficiency in removing lipids through beta-oxidation or efflux, the liver is overloaded with triglycerides in the form of lipid droplets in hepatocytes, leading to hepatic steatosis. The latter is the initial stage of nonalcoholic fatty liver disease (NAFLD) [5, 6]. NAFLD and NASH have been implicated as one of the most prevalent chronic liver diseases worldwide. The effective therapy for NASH is still not available [12, 13]

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