Transient impairment of the adaptive response to fasting in FXR-deficient mice.
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.
Cariou
Bertrand
B
Research Unit 545 INSERM, Atherosclerosis Department, Pasteur Institute of Lille, Faculty of Pharmacy, Lille2 University, Lille, France.
van Harmelen
Kirsten
K
Duran-Sandoval
Daniel
D
van Dijk
Theo
T
Grefhorst
Aldo
A
Bouchaert
Emmanuel
E
Fruchart
Jean-Charles
JC
Gonzalez
Frank J
FJ
Kuipers
Folkert
F
Staels
Bart
B
D000222:Adaptation, Physiological; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005215:Fasting; D005260:Female; D006706:Homeostasis; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
D017931:DNA Primers; D004268:DNA-Binding Proteins; D008112:Liver Glycogen; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated