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

    75 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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