title: Berberine ameliorates nonalcoholic fatty liver disease by a global modulation of hepatic mRNA and lncRNA expression profiles.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. yuanxinlu1982@126.com.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China. msswjw@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China. tangxy@sibs.ac.cn.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China. yxli@sibs.ac.cn.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. xiapu_fudan@163.com.
authors.forename: Pu
authors.initials: P
authors.lastname: Xia
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. happy20061208@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D059305:Diet, High-Fat; D005247:Feeding Behavior; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000235:genetics; D017207:Rats, Sprague-Dawley; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D001599:Berberine; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D014157:Transcription Factors; C427486:ZBTB20 protein, human; D051267:NF-E2-Related Factor 2