title: MiR-146b attenuates high-fat diet-induced non-alcoholic steatohepatitis in mice.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In this study, we investigated the role of miR-146b in the Toll-like receptor-4 signaling pathway and high-fat diet (HFD)-induced NASH in vivo and in vitro.
  
  
  METHODS
  The effect of miR-146b on the expression of IL-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in RAW264.7 cells and HepG2 was studied, and the effect of miR-146b on lipid accumulation in HepG2 was also studied in vitro. The levels of IRAK1, TRAF6, NF-κB, and pro-inflammatory cytokines, as well as the histologic features and lipid accumulation in the livers of HFD-induced non-alcoholic steatohepatitis (NASH) and an miR-146b-administered HFD mouse model, were studied in vivo.
  
  
  RESULTS
  After miR-146b administration, TRAF6 and IRAK1 mRNA and protein levels in macrophages after lipopolysaccharide administration and in HepG2 cells after oleic acid (OA) administration were significantly decreased in 146b group compared with control group (P < 0.001). The lipid accumulation in HepG2 cells exposed to OA was also decreased by inactivation of IRAK1 and TRAF6, then downregulation of the downstream molecules (NF-κB) and upregulation of the tension homolog deleted on chromosome 10 (PTEN) level. In vivo, after administration of miR-146b, TRAF6 and IRAK1 mRNA and protein levels as well as TNF-α and IL-6 mRNA and protein levels were decreased, and hematoxylin and eosin staining showed that the 146b group had low average adipose cell cross-sectional areas compared with control group.
  
  
  CONCLUSIONS
  MiR-146b ameliorated HFD-induced NASH by directly suppressing IRAK1 and TRAF6.
authors.affiliation: Institute of Pediatric Research, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China; Department of Neonatal Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Jiang
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Dai
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.forename: Chenling
authors.initials: C
authors.lastname: Ji
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage*; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000067996:RAW 264.7 Cells; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D018836:Inflammation Mediators; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse
keywords: IL-1 receptor-associated kinase 1 (IRAK1); Toll-like receptor signaling; miR-146b; non-alcoholic steatohepatitis; tumor necrosis factor receptor-associated factor 6 (TRAF6)