Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells

Kristoffer Niss, Magnus E. Jakobsson, David Westergaard, Kirstine González-Izarzugaza Belling, Jesper V. Olsen, Søren Brunak*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Activated transcription factor (TF) farnesoid X receptor (FXR) represses glucagon-like peptide-1 (GLP-1) secretion in enteroendocrine L cells. This, in turn, reduces insulin secretion, which is triggered when β cells bind GLP-1. Preventing FXR activation could boost GLP-1 production and insulin secretion. Yet, FXR's broader role in L cell biology still lacks understanding. Here, we show that FXR is a multifaceted TF in L cells using proteomics and gene expression data generated on GLUTag L cells. Most striking, 252 proteins regulated upon glucose stimulation have their abundances neutralized upon FXR activation. Mitochondrial repression or glucose import block are likely mechanisms of this. Further, FXR physically targets bile acid metabolism proteins, growth factors and other TFs, regulates ChREBP, while extensive text-mining found 30 FXR-regulated proteins to be well-known in L cell biology. Taken together, this outlines FXR as a powerful TF, where GLP-1 secretion block is just one of many downstream effects.
Original languageEnglish
Article number110923
JournalMolecular and Cellular Endocrinology
Volume517
Number of pages9
ISSN0303-7207
DOIs
Publication statusPublished - 2020

Keywords

  • Enteroendocrine L cells
  • Farnesoid X receptor
  • Glycolysis
  • Mitochondrial repression
  • Proteomics
  • Text-mining

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