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FEBS Lett. 2005 Aug 1;579(19):4076-80.

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

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Research Unit 545 INSERM, Atherosclerosis Department, Pasteur Institute of Lille, Faculty of Pharmacy, Lille2 University, Lille, France.


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.

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