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

Mar Drugs. 2019 Mar 19;17(3):181. doi: 10.3390/md17030181.

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.

Keywords: alcoholic liver disease; astaxanthin; bioinformatic analysis; comparative transcriptome analyses.

MeSH terms

  • Animals
  • Aquatic Organisms / chemistry*
  • Disease Models, Animal
  • Ethanol / administration & dosage
  • Ethanol / toxicity
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Liver Diseases, Alcoholic / drug therapy*
  • Liver Diseases, Alcoholic / etiology
  • Liver Diseases, Alcoholic / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Sequence Analysis, RNA
  • Signal Transduction / drug effects
  • Transcriptome / drug effects*
  • Treatment Outcome
  • Xanthophylls / pharmacokinetics
  • Xanthophylls / therapeutic use

Substances

  • Protective Agents
  • Xanthophylls
  • Ethanol
  • astaxanthine