Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells

Niss, Kristoffer ; Jakobsson, Magnus E. LU ; Westergaard, David ; Belling, Kirstine G. ; Olsen, Jesper V. and Brunak, Søren (2020) In Molecular and Cellular Endocrinology 517.
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Enteroendocrine L cells, Farnesoid X receptor, Glycolysis, Mitochondrial repression, Proteomics, Text-mining
in
Molecular and Cellular Endocrinology
volume
517
article number
110923
publisher
Elsevier
external identifiers
  • scopus:85088864665
  • pmid:32702472
ISSN
0303-7207
DOI
10.1016/j.mce.2020.110923
language
English
LU publication?
yes
id
e5b4ba31-4973-4b32-8c93-4ecf2898dd89
date added to LUP
2020-08-07 11:06:37
date last changed
2024-05-29 18:47:39
@article{e5b4ba31-4973-4b32-8c93-4ecf2898dd89,
  abstract     = {{<p>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.</p>}},
  author       = {{Niss, Kristoffer and Jakobsson, Magnus E. and Westergaard, David and Belling, Kirstine G. and Olsen, Jesper V. and Brunak, Søren}},
  issn         = {{0303-7207}},
  keywords     = {{Enteroendocrine L cells; Farnesoid X receptor; Glycolysis; Mitochondrial repression; Proteomics; Text-mining}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Molecular and Cellular Endocrinology}},
  title        = {{Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells}},
  url          = {{http://dx.doi.org/10.1016/j.mce.2020.110923}},
  doi          = {{10.1016/j.mce.2020.110923}},
  volume       = {{517}},
  year         = {{2020}},
}