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

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• 作者：Bertrand Cariou ; Kirsten van Harmelen ; Daniel Duran-Sandoval ; Theo van Dijk ; Aldo Grefhorst ; Emmanuel Bouchaert ; Jean-Charles Fruchart ; Frank J. Gonzalez ; Folkert Kuipers and Bart Staels
• 关键词：Farnesoid X receptor ; Fasting ; PEPCK ; Gluconeogenesis
• 刊名：FEBS Letters
• 出版年：2005
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：2005
• 卷：579
• 期：19
• 页码：4076-4080
• 文件大小：123 K

摘要

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 6 h of fasting and was decreased in FXR^−/−hepatocytes. FXR therefore plays an unexpected role in the control of fuel availability upon fasting.