Frontiers in Molecular Neuroscience (Jan 2022)

Farnesoid X Receptor Activation in Brain Alters Brown Adipose Tissue Function via the Sympathetic System

  • Benjamin Deckmyn,
  • Benjamin Deckmyn,
  • Benjamin Deckmyn,
  • Benjamin Deckmyn,
  • Benjamin Deckmyn,
  • Dorothée Domenger,
  • Dorothée Domenger,
  • Dorothée Domenger,
  • Dorothée Domenger,
  • Chloé Blondel,
  • Chloé Blondel,
  • Chloé Blondel,
  • Chloé Blondel,
  • Sarah Ducastel,
  • Sarah Ducastel,
  • Sarah Ducastel,
  • Sarah Ducastel,
  • Emilie Nicolas,
  • Emilie Nicolas,
  • Emilie Nicolas,
  • Emilie Nicolas,
  • Emilie Dorchies,
  • Emilie Dorchies,
  • Emilie Dorchies,
  • Emilie Dorchies,
  • Emilie Caron,
  • Julie Charton,
  • Julie Charton,
  • Julie Charton,
  • Emmanuelle Vallez,
  • Emmanuelle Vallez,
  • Emmanuelle Vallez,
  • Emmanuelle Vallez,
  • Benoit Deprez,
  • Benoit Deprez,
  • Benoit Deprez,
  • Jean-Sébastien Annicotte,
  • Sophie Lestavel,
  • Sophie Lestavel,
  • Sophie Lestavel,
  • Sophie Lestavel,
  • Anne Tailleux,
  • Anne Tailleux,
  • Anne Tailleux,
  • Anne Tailleux,
  • Christophe Magnan,
  • Christophe Magnan,
  • Bart Staels,
  • Bart Staels,
  • Bart Staels,
  • Bart Staels,
  • Kadiombo Bantubungi,
  • Kadiombo Bantubungi,
  • Kadiombo Bantubungi,
  • Kadiombo Bantubungi

DOI
https://doi.org/10.3389/fnmol.2021.808603
Journal volume & issue
Vol. 14

Abstract

Read online

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. 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. 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. 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.

Keywords