A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis

  1. Feifan Guo1,*
  1. 1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, the Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences;
  2. 2Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University;
  3. 3Institutes of Biomedical Sciences, Fudan University;
  4. 4Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital affiliated Shanghai Jiaotong University School of Medicine;
  5. 5Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Shanghai Jiaotong University
  1. *Corresponding author: Feifan Guo, E-mail: ffguo{at}sibs.ac.cn
  1. # Fei Xiao and Junjie Yu contributed equally to this study

Abstract

MicroRNAs (miRNAs) are endogenous non-coding short single-stranded RNAs that are evolutionarily conserved and believed to play a role in controlling a variety of biological processes. The roles of miRNAs in insulin resistance and liver steatosis, however, are largely unknown. The objective of this study was to evaluate the roles of miR-130a in the regulation of insulin sensitivity and liver steatosis. In our current study, we observed that overexpression of miR-130a-3p increases insulin signaling in both HepG2 cells and primary mouse hepatocytes and silencing of miR-130a-3p has the opposite effects. However, miR-130a-5p has no effect in the regulation of insulin signaling. Consistently, whole body and hepatic insulin sensitivity is improved in mice injected with adenoviruses that over-express miR-130a-3p. Furthermore, we provided evidence showing that growth factor receptor-bound protein 10 is required for miR-130a-3p-regulated insulin sensitivity. On the other hand, we observed that expression of miR-130a-3p is decreased in the livers of db/db mice and that adenovirus-mediated overexpression of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of which is achieved via suppressing fatty acid synthase expression in these mice. This study identifies a novel function for hepatic miR-130a-3p in the regulation of insulin sensitivity and liver steatosis.

  • Received November 2, 2013.
  • Accepted March 22, 2014.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

This Article

  1. Diabetes
  1. Supplementary Data
  2. All Versions of this Article:
    1. db13-1689v1
    2. 63/8/2631 most recent