title: Aberrant hepatic microRNA expression in nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4- and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).
  
  
  RESULTS
  Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change >1.5) and 12 down-regulated miRNAs (fold change <0.5). Among the abnormally expressed miRNAs, miR-200a, miR-200b, miR-200c, miR-146a, miR-146b and miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors.
  
  
  CONCLUSIONS
  These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD.
authors.affiliation: Department of Endocrinology, the Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yue Ying
authors.initials: YY
authors.lastname: Feng
authors.forename: Xiao Qin
authors.initials: XQ
authors.lastname: Xu
authors.forename: Chen Bo
authors.initials: CB
authors.lastname: Ji
authors.forename: Chun Mei
authors.initials: CM
authors.lastname: Shi
authors.forename: Xi Rong
authors.initials: XR
authors.lastname: Guo
authors.forename: Jun Fen
authors.initials: JF
authors.lastname: Fu
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051381:Rats
chemical_list: D005230:Fatty Acids, Nonesterified; D035683:MicroRNAs