Background: Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder that currently lacks effective treatment. Berberine (BBR), a botanic compound isolated from traditional Chinese medicine, exhibits a potent therapeutic potential for the metabolic disease. The current study aimed to understand the mechanisms underlying the therapeutic effect of BBR in NAFLD. Methods: We performed systematical analyses on hepatic expression profiles of mRNAs and long noncoding RNAs (lncRNAs) in a high-fat diet (HFD)-induced steatotic animal model with or without BBR treatment. The study was conducted by using the methods of bioinformatics, including hierarchical clustering, gene enrichment and gene co-expression networks analysis. The effect of BBR on the expression profile of some interesting genes was confirmed by quantitative RT-PCR and further studied in a human hepatic cell line, Huh7. Results: We found that a large group of genes including 881 mRNAs and 538 lncRNAs whose expression in the steatotic liver was reversed by BBR treatment, suggesting a global effect of BBR in modulating hepatic gene expression profiles. Among the BBR-regulated genes, we identified several modules and numerous significant genes that were associated with liver metabolism and NAFLD-related functions. Specifically, a conserved lncRNA, MRAK052686, was found strongly correlated with the antioxidant factor Nrf2, and both genes were down-regulated by the steatotic liver. Moreover, the reduced expression of MRAK052686 and Nrf2 was completely reversed by BBR treatment, suggesting a new mechanism accounting for the therapeutic effect of BBR. Conclusions: The findings for the first time provide a new genetic insight into the pharmaceutical mechanism of BBR in protecting against NAFLD.
[1]Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai 200433, Peoples R China.
[2]Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Syst Biol, Shanghai, Peoples R China.
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