New insights in the multiple roles of bile acids and their signaling pathways in metabolic control

Jan F de Boer, Vincent W Bloks, Esther Verkade, M Rebecca Heiner-Fokkema, Folkert Kuipers*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: There is a growing awareness that individual bile acid species exert different physiological functions, beyond their classical roles in bile formation and fat absorption, due to differential stimulatory effects on the bile-acid-activated receptors farnesoid X receptor (FXR) and takeda G receptor 5 (TGR5). This review integrates recent findings on the role of individual bile acids and their receptors in metabolic control, with special emphasis on cholesterol homeostasis.

RECENT FINDINGS: The consequences of altered bile acid metabolism, for example, in type 2 diabetes and during aging, on metabolic control is increasingly recognized but full impact hereof remains to be elucidated. These effects interact with those of newly developed pharmacological FXR and TGR5 modulators that aim to improve metabolic health. Studies in genetically modified mice have provided important new insights, for example, establishment of the role of intestinal FXR in control of the transintestinal cholesterol excretion pathway. However, translation from mice to men is hampered by the presence of rodent-specific bile acid species with special features.

SUMMARY: Specific bile acids and their signaling pathways play important roles in control of (cholesterol) metabolism. Deeper insight into the interactions between endogenous (i.e., bile acids) and pharmacological modulators of FXR and TGR5 is needed to optimize therapeutic benefit of the latter. The recent identification of cytochrome P450 2C70 as key enzyme in the formation of rodent-specific hydrophilic muricholic acids allows for the development of adequate mouse models for this purpose.

Original languageEnglish
Pages (from-to)194-202
Number of pages9
JournalCurrent Opinion in Lipidology
Volume29
Issue number3
Early online date16-Mar-2018
DOIs
Publication statusPublished - Jun-2018

Keywords

  • bile acids
  • cytochrome P450
  • farnesoid X receptor
  • takeda G receptor 5
  • FARNESOID X RECEPTOR
  • 7 ALPHA-HYDROXYLASE
  • Y GASTRIC BYPASS
  • CHOLESTEROL ABSORPTION
  • NEONATAL CHOLESTASIS
  • MASS-SPECTROMETRY
  • OBETICHOLIC ACID
  • GLYCEMIC CONTROL
  • LIVER-DISEASE
  • LIFE-SPAN

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