Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes

FEBS Lett. 2009 Sep 3;583(17):2882-6. doi: 10.1016/j.febslet.2009.07.053. Epub 2009 Aug 4.

Abstract

Fibroblast growth factor 21 (FGF21) has beneficial effects of improving the plasma glucose and lipid profiles in diabetic rodents. Here, we investigated carbohydrate response element binding protein (ChREBP) involvement in the regulation of FGF21 mRNA expression in liver. Glucose stimulation and adenoviral overexpression of dominant active ChREBP increased FGF21 mRNA. Consistently, adenoviral expression of dominant negative Mlx inhibited glucose induction of FGF21 mRNA. Furthermore, deletion studies of mouse FGF21 gene promoter (-2000 to +65 bp) revealed a glucose responsive region between -74 and -52 bp. These findings suggest that FGF21 expression is regulated by ChREBP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cells, Cultured
  • Fibroblast Growth Factors* / genetics
  • Fibroblast Growth Factors* / metabolism
  • Glucose / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Mice
  • Promoter Regions, Genetic
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Rats
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Activation

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MLX protein, rat
  • Mlxipl protein, rat
  • RNA, Messenger
  • Trans-Activators
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Glucose