NS5ATP6 modulates intracellular triglyceride content through FGF21 and independently of SIRT1 and SREBP1

Biochem Biophys Res Commun. 2016 Jun 17;475(1):133-9. doi: 10.1016/j.bbrc.2016.05.056. Epub 2016 May 11.

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising strikingly in Western countries and China. The molecular biological mechanism of NAFLD remains unclear, with no effective therapies developed so far. Fibroblast growth factor 21 (FGF21) is a recently discovered hormone, with safe lipid lowering effects. FGF21 analogs are being developed for clinical application. Here we demonstrated that a novel gene, NS5ATP6, modulated intracellular triglyceride (TG) content independently of sirtuin1 (SIRT1) and sterol regulatory element binding protein 1 (SREBP1) in HepG2 cells. Interestingly, NS5ATP6 regulated FGF21 expression both at the mRNA and protein levels. The modulatory effects of NS5ATP6 on intracellular TG content depended upon FGF21. Further studies revealed that NS5ATP6 decreased the promoter activity of FGF21. In addition, NS5ATP6 regulated the expression of miR-577, which directly targeted and regulated FGF21. Therefore, miR-577 might be involved in NS5ATP6 regulation of FGF21 at the post-transcriptional level. In conclusion, NS5ATP6 regulates the intracellular TG level via FGF21, and independently of SIRT1 and SREBP1.

Keywords: FGF21; NS5ATP6; SIRT1; SREBP1; miR-577.

MeSH terms

  • Carrier Proteins / metabolism*
  • Cholesterol / metabolism
  • DNA-Binding Proteins
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation
  • Hep G2 Cells
  • Humans
  • Liver / metabolism*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Sirtuin 1 / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / metabolism*
  • Triglycerides / metabolism*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • PCLAF protein, human
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Cholesterol
  • Sirtuin 1