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Crosstalk between FXR and TGR5 controls glucagon-like peptide 1 secretion to maintain glycemic homeostasis

Hyeonhui Kim1, Sungsoon Fang1

  • 1Severance Biomedical Science Institute, BK21 PLUS project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Laboratory Animal Research
|January 24, 2019
PubMed

Insights

Bile acids act as hormones, regulating metabolism via Farnesoid X receptor (FXR) and TGR5. Targeting these receptors may treat metabolic diseases like type II diabetes.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Molecular Biology

Background:

  • Bile acids, traditionally known as digestive juices, are increasingly recognized for their hormonal roles.
  • They interact with receptors like Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5), influencing numerous biological processes.
  • Dysfunction of these receptors is linked to metabolic disorders such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance.

Purpose of the Study:

  • To explore the role of bile acid signaling pathways in metabolic regulation.
  • To investigate the therapeutic potential of bile acid receptors (FXR and TGR5) in metabolic diseases, particularly type II diabetes.

Main Methods:

  • Review of recent scientific literature on bile acid signaling and metabolic regulation.
  • Analysis of studies investigating the interaction between bile acids, their receptors (FXR, TGR5), and metabolic pathways.
  • Examination of the link between bile acid signaling alterations and type II diabetes.

Main Results:

  • Bile acids function as hormones, modulating cholesterol, glucose, and lipid metabolism, as well as immune and energy balance.
  • Deficiency in FXR and TGR5 is associated with the development of metabolic syndromes.
  • Activation of TGR5 by bile acids enhances glucagon-like peptide 1 (GLP-1) secretion, improving insulin secretion.
  • FXR and TGR5 exhibit crosstalk, collectively influencing GLP-1 secretion.

Conclusions:

  • Bile acid receptors FXR and TGR5 play critical roles in maintaining metabolic homeostasis.
  • Alterations in bile acid signaling pathways are implicated in type II diabetes.
  • FXR and TGR5 represent promising therapeutic targets for managing metabolic diseases, including type II diabetes.
Keywords:
Bile acidsFarnesoid X receptorG protein-coupled bile acid receptorGlucagon-like peptide 1diabetesobesity

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