Transient impairment of the adaptive response to fasting in FXR-deficient mice

FEBS Lett. 2005 Aug 1;579(19):4076-80. doi: 10.1016/j.febslet.2005.06.033.


The farnesoid X receptor (FXR) has been suggested to play a role in gluconeogenesis. To determine whether FXR modulates the response to fasting in vivo, FXR-deficient (FXR-/-) and wild-type mice were submitted to fasting for 48 h. Our results demonstrate that FXR modulates the kinetics of alterations of glucose homeostasis during fasting, with FXR-/- mice displaying an early, accelerated hypoglycaemia response. Basal hepatic glucose production rate was lower in FXR-/- mice, together with a decrease in hepatic glycogen content. Moreover, hepatic PEPCK gene expression was transiently lower in FXR-/- mice after 6h of fasting and was decreased in FXR-/- hepatocytes. FXR therefore plays an unexpected role in the control of fuel availability upon fasting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Base Sequence
  • DNA Primers
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Fasting*
  • Female
  • Homeostasis
  • Liver / enzymology
  • Liver / metabolism
  • Liver Glycogen / metabolism
  • Mice
  • Mice, Knockout
  • Phosphoenolpyruvate Carboxykinase (ATP) / genetics
  • Receptors, Cytoplasmic and Nuclear
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • DNA Primers
  • DNA-Binding Proteins
  • Liver Glycogen
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • farnesoid X-activated receptor
  • Phosphoenolpyruvate Carboxykinase (ATP)