A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis
- Fei Xiao1,#,
- Junjie Yu1,#,
- Bin Liu1,
- Yajie Guo1,
- Kai Li1,
- Jiali Deng1,
- Jin Zhang2,3,
- Chunxia Wang1,
- Shanghai Chen1,
- Ying Du1,
- Yingli Lu4,
- Yuzhong Xiao1,
- Zhou Zhang5 and
- Feifan Guo1,*
- 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;
- 2Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University;
- 3Institutes of Biomedical Sciences, Fudan University;
- 4Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital affiliated Shanghai Jiaotong University School of Medicine;
- 5Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Shanghai Jiaotong University
- *Corresponding author: Feifan Guo, E-mail:
# Fei Xiao and Junjie Yu contributed equally to this study
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.
- © 2014 by the American Diabetes Association.
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