Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice.

Abstract

BACKGROUND/AIMS:

Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention.

METHODS:

The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique.

RESULTS:

A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases.

CONCLUSIONS:

The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD.

• Authors: Jun Guo, Yuan Zhou, Yafen Cheng, Weiwei Fang, Gang Hu, Jie Wei, Yajun Lin, Yong Man, Lixin Guo, Mingxiao Sun, Qinghua Cui, Jian Li
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 45 Issue 4 Pg. 1487-1505 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29466788 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• MicroRNAs
• RNA, Circular
• RNA, Long Noncoding
• RNA, Messenger
• Triglycerides
• RNA
• Metformin
• AMP-Activated Protein Kinases
• Acetyl-CoA Carboxylase

Topics

• AMP-Activated Protein Kinases (metabolism)
• Acetyl-CoA Carboxylase (metabolism)
• Animals
• Diet, High-Fat
• Disease Models, Animal
• Gene Regulatory Networks (drug effects)
• Liver (drug effects, metabolism, pathology)
• Male
• Metformin (pharmacology)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (metabolism)
• Non-alcoholic Fatty Liver Disease (genetics, metabolism, pathology)
• Oligonucleotide Array Sequence Analysis
• Phosphorylation (drug effects)
• Principal Component Analysis
• RNA (metabolism)
• RNA, Circular
• RNA, Long Noncoding (metabolism)
• RNA, Messenger (metabolism)
• Transcriptome (drug effects)
• Triglycerides (analysis)