title: MicroRNA-185 regulates expression of lipid metabolism genes and improves insulin sensitivity in mice with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  To assess the regulatory effect of microRNA-185 (miR-185) on lipid metabolism and the insulin signalling pathway in human HepG2 hepatocytes and a high-fat diet mouse model.
  
  
  METHODS
  Quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA levels of lipogenic genes after loss or gain of miR-185. In addition, the amounts of insulin signalling intermediates were determined after transfection of HepG2 cells with pre-miR-185.
  
  
  RESULTS
  MiR-185 levels decreased in a time- and dose-dependent manner in response to palmitic acid in human HepG2 hepatocytes. Transfection of HepG2 cells with miR-185 significantly decreased the mRNA levels of fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, sterol-regulatory element binding protein-2, and sterol-regulatory element binding protein-1c, whereas inhibition of miR-185 using an anti-miR-185 oligonucleotide produced the opposite effect in HepG2 cells. In a high-fat diet mouse model, the accumulation of lipids was significantly improved after treatment with miR-185, compared with control animals. Induction of miR-185 enhanced the insulin signalling pathway by up-regulating the insulin-receptor substrate-2.
  
  
  CONCLUSIONS
  These findings suggest that miR-185 plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes, as well as in improving insulin sensitivity, both in vitro and in vivo.
authors.affiliation: Xiao-Chen Wang, Xiao-Rong Zhan, Xin-Yu Li, Jun-Jie Yu, Xiao-Min Liu, Department of Endocrinology, First Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Wang
authors.affiliation: Xiao-Chen Wang, Xiao-Rong Zhan, Xin-Yu Li, Jun-Jie Yu, Xiao-Min Liu, Department of Endocrinology, First Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Zhan
authors.affiliation: Xiao-Chen Wang, Xiao-Rong Zhan, Xin-Yu Li, Jun-Jie Yu, Xiao-Min Liu, Department of Endocrinology, First Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: Xiao-Chen Wang, Xiao-Rong Zhan, Xin-Yu Li, Jun-Jie Yu, Xiao-Min Liu, Department of Endocrinology, First Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Xiao-Chen Wang, Xiao-Rong Zhan, Xin-Yu Li, Jun-Jie Yu, Xiao-Min Liu, Department of Endocrinology, First Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Liu
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000097:blood; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D005227:Fatty Acids; D007328:Insulin; C552431:MIRN185 microRNA, human; D035683:MicroRNAs; C578934:Mirn185 microRNA, mouse; D012333:RNA, Messenger; D002784:Cholesterol
keywords: Insulin signalling pathway; Lipid metabolism; MiR-185; Non-alcoholic fatty liver disease