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Farnesoid X Receptor activation in brain alters brown adipose tissue function via the sympathetic system
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  • Benjamin Deckmyn,
  • Dorothee Domenger,
  • sarah ducatsel,
  • emilie nicolas,
  • emilie dorchies,
  • emilie caron,
  • julie charton,
  • emmanuelle vallez,
  • benoit deprez,
  • jean-sebastien annicotte,
  • sophie lestavel,
  • anne tailleux,
  • christophe magnan,
  • Bart Staels,
  • Kadiombo Bantubungi
Benjamin Deckmyn
Inserm U1011
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Dorothee Domenger
Inserm U1011
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sarah ducatsel
Inserm U1011
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emilie nicolas
Inserm U1011
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emilie dorchies
Université de Lille
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emilie caron
Université de Lille
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julie charton
Université de Lille
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emmanuelle vallez
Inserm U1011
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benoit deprez
Université de Lille
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jean-sebastien annicotte
umr 8199
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sophie lestavel
Inserm U1011
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anne tailleux
Inserm U1011
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christophe magnan
UMR8251
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Bart Staels
Université de Lille
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Kadiombo Bantubungi
Université de Lille
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Abstract

Background and Prupose: The nuclear bile acid (BA) receptor farnesoid X receptor (FXR) is a major regulator of metabolic/energy homeostasis in peripheral organs. Indeed, enterohepatic-expressed FXR controls metabolic processes (BA, glucose and lipid metabolism, fat mass, body weight). The central nervous system (CNS) regulates energy homeostasis in close interaction with peripheral organs. While FXR has been reported to be expressed in the brain, its function has not been studied so far. Experimental Approach: We studied the role of FXR in brain control of energy homeostasis by treating wild-type and FXR-deficient mice by intracerebroventricular (ICV) injection with the reference FXR agonist GW4064. Key Results: Here we show that pharmacological activation of brain FXR modifies energy homeostasis by affecting brown adipose tissue (BAT) function. Brain FXR activation decreases the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and consequently the sympathetic tone. FXR activation acts by inhibiting hypothalamic PKA-CREB induction of TH expression. Conclusions and Implication: These findings identify a function of brain FXR in the control of energy homeostasis and shed new light on the complex control of energy homeostasis by BA through FXR.

Peer review status:UNDER REVIEW

08 May 2021Submitted to British Journal of Pharmacology
10 May 2021Assigned to Editor
10 May 2021Submission Checks Completed
20 May 2021Reviewer(s) Assigned