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

Bertrand Cariou; Kirsten Van Harmelen; Daniel Duran-Sandoval; Theo Van Dijk; Aldo Grefhorst; Emmanuel Bouchaert; Jean Charles Fruchart; Frank J. Gonzalez; Folkert Kuipers; Bart Staels

doi:10.1016/j.febslet.2005.06.033

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

Bertrand Cariou, Kirsten Van Harmelen, Daniel Duran-Sandoval, Theo Van Dijk, Aldo Grefhorst, Emmanuel Bouchaert, Jean Charles Fruchart, Frank J. Gonzalez, Folkert Kuipers, Bart Staels

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76 Scopus citations

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 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.

Original language	English
Pages (from-to)	4076-4080
Number of pages	5
Journal	FEBS Letters
Volume	579
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2005.06.033
State	Published - 1 Aug 2005
Externally published	Yes

Keywords

Farnesoid X receptor
Fasting
Gluconeogenesis
PEPCK

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10.1016/j.febslet.2005.06.033

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title = "Transient impairment of the adaptive response to fasting in FXR-deficient mice",

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 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.",

keywords = "Farnesoid X receptor, Fasting, Gluconeogenesis, PEPCK",

author = "Bertrand Cariou and {Van Harmelen}, Kirsten and Daniel Duran-Sandoval and {Van Dijk}, Theo and Aldo Grefhorst and Emmanuel Bouchaert and Fruchart, {Jean Charles} and Gonzalez, {Frank J.} and Folkert Kuipers and Bart Staels",

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AU - Cariou, Bertrand

AU - Van Harmelen, Kirsten

AU - Duran-Sandoval, Daniel

AU - Van Dijk, Theo

AU - Grefhorst, Aldo

AU - Bouchaert, Emmanuel

AU - Fruchart, Jean Charles

AU - Gonzalez, Frank J.

AU - Kuipers, Folkert

AU - Staels, Bart

PY - 2005/8/1

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N2 - 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.

AB - 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.

KW - Farnesoid X receptor

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KW - Gluconeogenesis

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

Abstract

Keywords

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