MicroRNA-190b regulates lipid metabolism and insulin sensitivity by targeting IGF-1 and ADAMTS9 in non-alcoholic fatty liver disease.

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  • Author(s): Xu M;Xu M; Zheng XM; Zheng XM; Jiang F; Qiu WQ
  • Source:
    Journal of cellular biochemistry [J Cell Biochem] 2018 Jul; Vol. 119 (7), pp. 5864-5874. Date of Electronic Publication: 2018 Mar 25.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8205768 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4644 (Electronic) Linking ISSN: 07302312 NLM ISO Abbreviation: J Cell Biochem Subsets: MEDLINE
    • Publication Information:
      Publication: <2004>- : Hoboken, NJ : Wiley-Liss
      Original Publication: New York : Liss, c1982-
    • Subject Terms:
      Insulin Resistance* ; Lipid Metabolism*; ADAMTS9 Protein/*metabolism ; Insulin-Like Growth Factor I/*metabolism ; MicroRNAs/*genetics ; Non-alcoholic Fatty Liver Disease/*pathology; ADAMTS9 Protein/genetics ; Animals ; Case-Control Studies ; Cells, Cultured ; Disease Models, Animal ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Humans ; Insulin-Like Growth Factor I/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Signal Transduction
    • Abstract:
      Nonalcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid accumulation and insulin resistance, yet the underlying molecular mechanisms are poorly understood. MiR-190b is thought to play a role in hepatocellular carcinoma by modulating insulin resistance; however, its role in NAFLD remains unknown. Here, we found that miR-190b expression was significantly increased in the liver tissues of patients with NAFLD, compared to normal tissues. Moreover, miR-190b was upregulated in a high-fat diet NAFLD mouse model and a free fatty acid-induced NAFLD cellular model. Knockdown of miR-190b decreased aspartate transaminase (AST), alanine transaminase (ALT), triglyceride (TG), and total cholesterol (TC). It also reduced expression of the lipogenic genes fatty acid synthase (FAS) and 3-hydroxy-3-methylglutarylCoA reductase (HMGCR), alleviated hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in vitro. Furthermore, we confirmed that miR-190b directly targeted IGF-1 and ADAMTS9. MiR-190b overexpression suppressed expression of IGF-1 and ADAMTS9, which were increased by miR-190b inhibition. Expression of IGF-1 and ADAMTS9 was inversely correlated with miR-190b in liver tissues of patients with NAFLD, respectively. We also found that IGF-1 or ADAMTS9 inhibition partially reversed the effects of miR-190b on lipid metabolism and insulin signaling in vitro. Taken together, the data reveal that miR-190b inhibition suppressed lipid accumulation and improved insulin sensitivity by targeting IGF-1 and ADAMTS9, suggesting that miR-190b inhibition may be a therapeutic strategy against NAFLD.
      (© 2018 Wiley Periodicals, Inc.)
    • Contributed Indexing:
      Keywords: ADAMTS9; IGF-1; MicroRNA-190b; NAFLD; insulin resitance; lipid metabolism
    • Accession Number:
      0 (IGF1 protein, human)
      0 (MIRN190 microRNA, human)
      0 (MicroRNAs)
      67763-96-6 (Insulin-Like Growth Factor I)
      EC 3.4.24.- (ADAMTS9 Protein)
      EC 3.4.24.- (ADAMTS9 protein, human)
    • Publication Date:
      Date Created: 20180326 Date Completed: 20190508 Latest Revision: 20190508
    • Publication Date:
      20221213
    • Accession Number:
      10.1002/jcb.26776
    • Accession Number:
      29575055