Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells
(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.
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- author
- Niss, Kristoffer ; Jakobsson, Magnus E. LU ; Westergaard, David ; Belling, Kirstine G. ; Olsen, Jesper V. and Brunak, Søren
- organization
- publishing date
- 2020
- 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
- 2024-09-19 04:51:55
@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}}, }