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Updated: Dec 14, 2025

Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
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Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells

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Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells

Kristoffer Niss1, Magnus E Jakobsson2, David Westergaard3

  • 1Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.

Molecular and Cellular Endocrinology
|July 24, 2020
PubMed

Insights

Farnesoid X receptor (FXR) is a powerful transcription factor in gut L cells, controlling more than just glucagon-like peptide-1 (GLP-1) secretion. Understanding FXR

Area of Science:

  • Endocrinology and Metabolism
  • Cell Biology
  • Molecular Biology

Background:

  • The transcription factor farnesoid X receptor (FXR) is known to inhibit glucagon-like peptide-1 (GLP-1) secretion from enteroendocrine L cells.
  • This inhibition of GLP-1 reduces insulin secretion, impacting glucose homeostasis.
  • The comprehensive role of FXR in L cell biology remains largely unexplored.

Purpose of the Study:

  • To elucidate the multifaceted role of FXR as a transcription factor in enteroendocrine L cells.
  • To identify novel FXR-regulated pathways and proteins within L cells beyond GLP-1 regulation.

Main Methods:

  • Proteomics and gene expression analysis were performed on GLUTag L cells.
  • Analysis focused on proteins and gene expression changes upon glucose stimulation and FXR activation.
  • Text-mining was employed to identify known L cell biology proteins regulated by FXR.

Main Results:

  • FXR activation neutralized the abundance of 252 proteins regulated by glucose stimulation in L cells.
  • Potential mechanisms for FXR's effect include mitochondrial repression and impaired glucose import.
  • FXR was found to physically interact with proteins involved in bile acid metabolism, growth factors, and other transcription factors, including ChREBP.

Conclusions:

  • FXR is a significant regulator of L cell biology, with broad downstream effects.
  • The repression of GLP-1 secretion is only one aspect of FXR's extensive influence on L cells.
  • FXR's regulation of numerous proteins highlights its critical role in L cell function and potentially in metabolic regulation.
Keywords:
Enteroendocrine L cellsFarnesoid X receptorGlycolysisMitochondrial repressionProteomicsText-mining

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