MicroRNA-199a Targets the Fatty Acid Transport Protein 1 Gene and Inhibits the Adipogenic Trans-Differentiation of C2C12 Myoblasts

Cell Physiol Biochem. 2016;39(3):1087-97. doi: 10.1159/000447817. Epub 2016 Aug 26.

Abstract

Background/aims: Muscle cells are able to trans-differentiate into adipocytes with adipogenesis induction. MicroRNAs (miRNAs), a class of small non-coding RNAs, widely participate in the regulation of growth and development of cells. However, the expression and regulatory role of miRNAs in the trans-differentiation of muscle cell are largely unknown.

Methods: C2C12 myoblasts were inducted to adipogenesis trans-differentiation and microarrays were used to assay the changes of expression profile of miRNAs. MiR-199a, a miRNA showed significant change in the trans-differentiation, was selected for the subsequent function study via over- expression and knock down.

Results: Dozens of miRNAs showed different changes followed the adipogenesis trans-differentiation of C2C12 cells. In which, miR-199a was decreased in the adipogenic cells and miR-199a over-expression inhibited the trans-differentiation and decreased lipid accumulation in the cells. Moreover, Fatty acid transport protein 1 (Fatp1), a major regulator of trans-membrane transportation and the oxidative metabolism of free fatty acids, was showed to be a target of miR-199a by computational and luciferase reporter assays. Additionally, Fatp1 knock-down by small interfering RNA had similar inhibitory effects on the trans-differentiation in C2C12 cells.

Conclusion: Our study reveals an important role for miR-199a in the regulation of adipogenic trans-differentiation in muscle cells via suppression of Fatp1 gene.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adipogenesis / genetics*
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Transdifferentiation / genetics*
  • Fatty Acid Transport Proteins / antagonists & inhibitors
  • Fatty Acid Transport Proteins / genetics*
  • Fatty Acid Transport Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genes, Reporter
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Fatty Acid Transport Proteins
  • MicroRNAs
  • Mirn199 microRNA, mouse
  • RNA, Small Interfering
  • Slc27a1 protein, mouse
  • Luciferases