Comparative Transcriptome Analyses Provide Potential Insights into the Molecular Mechanisms of Astaxanthin in the Protection against Alcoholic Liver Disease in Mice.

Huilin Liu,Jingsheng Liu,Xueqi Fu,Lingyu Zhu,Ziqi Zhang,Huimin Liu,Xin Zheng

doi:10.3390/md17030181

Huilin Liu, Jingsheng Liu + Show 5 more

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https://doi.org/10.3390/md17030181

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Abstract

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. It is a complex process, including a broad spectrum of hepatic lesions from fibrosis to cirrhosis. Our previous study suggested that astaxanthin (AST) could alleviate the hepatic inflammation and lipid dysmetabolism induced by ethanol administration. In this study, a total of 48 male C57BL/6J mice were divided into 4 groups: a Con group (fed with a Lieber–DeCarli liquid diet), an AST group (fed with a Lieber–DeCarli liquid diet and AST), an Et group (fed with an ethanol-containing Lieber–DeCarli liquid diet), and a EtAST group (fed with an ethanol-containing Lieber–DeCarli liquid diet and AST). Then, comparative hepatic transcriptome analysis among the groups was performed by Illumina RNA sequencing. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of the top genes were verified by quantitative real-time PCR (qRT-PCR) and Western blot. A total of 514.95 ± 6.89, 546.02 ± 15.93, 576.06 ± 21.01, and 690.85 ± 54.14 million clean reads were obtained for the Con, AST, Et, and EtAST groups, respectively. Compared with the Et group, 1892 differentially expressed genes (DEGs) (including 351 upregulated and 1541 downregulated genes) were identified in the AST group, 1724 differentially expressed genes (including 233 upregulated and 1491 downregulated genes) were identified in the Con group, and 1718 DEGs (including 1380 upregulated and 338 downregulated genes) were identified in the EtAST group. The enrichment analyses revealed that the chemokine signaling, the antigen processing and presentation, the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, and the Toll-like receptor signaling pathways enriched the most differentially expressed genes. The findings of this study provide insights for the development of nutrition-related therapeutics for ALD.

Highlights

A recent report from the World Health Organization indicates that three million deaths every year result from the harmful use of alcohol [1,2]
The enrichment analyses revealed that the chemokine signaling, the antigen processing and presentation, the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, and the Toll-like receptor signaling pathways enriched the most differentially expressed genes
Through nucleotide basic local alignment search tool (BLAST) analysis, more than 97% of the reads of each group were mapped to known genes, and more than 95% of the reads were mapped to exons

Summary

Introduction

A recent report from the World Health Organization indicates that three million deaths every year result from the harmful use of alcohol (representing 5.3% of all global deaths) [1,2]. Mar. Drugs 2019, 17, 181 one of the leading causes of more than 200 disease and injury conditions worldwide [3]. As the liver is the major organism for the metabolism of alcohol, long-term use and over-consumption of alcohol leads to alcoholic liver disease (ALD). The pathogenesis of ALD has been well characterized, but no specific drugs and therapy were available to reverse this progress in humans. Recent studies showed that some intracellular signaling pathways and transcriptional factors are involved in the mechanisms of pathogenesis of ALD [7]

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