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

B Cariou, K van Harmelen, D Duran-Sandoval, T van Dijk, A Grefhorst, E Bouchaert, JC Fruchart, FJ Gonzalez, F Kuipers, B Staels*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

71 Citations (Scopus)

Abstract

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 transient lower in FXR(-/-)mice after 6 h of fasting and was decreased in FXR(-/-)hepatocytes. FXR therefore plays an unexpected role in the control of fuel availability upon fasting. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)4076-4080
Number of pages5
JournalFEBS Letters
Volume579
Issue number19
DOIs
Publication statusPublished - 1-Aug-2005

Keywords

  • farnesoid X receptor
  • fasting
  • PEPCK
  • gluconeogenesis
  • FARNESOID-X-RECEPTOR
  • PHOSPHOENOLPYRUVATE CARBOXYKINASE
  • BILE-ACIDS
  • METABOLISM
  • LIVER
  • GLUCONEOGENESIS
  • HOMEOSTASIS
  • INHIBITION
  • EXPRESSION
  • CYCLE

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