title: Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity.
abstract: OBJECTIVE
  Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role of FXR in obesity and associated complications, such as dyslipidemia and insulin resistance, has not been directly assessed.
  
  
  METHODS
  Here, we evaluate the consequences of FXR deficiency on body weight development, lipid metabolism, and insulin resistance in murine models of genetic and diet-induced obesity.
  
  
  RESULTS
  FXR deficiency attenuated body weight gain and reduced adipose tissue mass in both models. Surprisingly, glucose homeostasis improved as a result of an enhanced glucose clearance and adipose tissue insulin sensitivity. In contrast, hepatic insulin sensitivity did not change, and liver steatosis aggravated as a result of the repression of β-oxidation genes. In agreement, liver-specific FXR deficiency did not protect from diet-induced obesity and insulin resistance, indicating a role for nonhepatic FXR in the control of glucose homeostasis in obesity. Decreasing elevated plasma BA concentrations in obese FXR-deficient mice by administration of the BA sequestrant colesevelam improved glucose homeostasis in a FXR-dependent manner, indicating that the observed improvements by FXR deficiency are not a result of indirect effects of altered BA metabolism.
  
  
  CONCLUSIONS
  Overall, FXR deficiency in obesity beneficially affects body weight development and glucose homeostasis.
authors: University of Lille Nord de France, INSERM UMR1011, UDSL, Institut Pasteur de Lille, Lille, France.
authors: Janne
authors: J
authors: Prawitt
authors: Mouaadh
authors: M
authors: Abdelkarim
authors: Johanna H M
authors: JH
authors: Stroeve
authors: Iuliana
authors: I
authors: Popescu
authors: Helene
authors: H
authors: Duez
authors: Vidya R
authors: VR
authors: Velagapudi
authors: Julie
authors: J
authors: Dumont
authors: Emmanuel
authors: E
authors: Bouchaert
authors: Theo H
authors: TH
authors: van Dijk
authors: Anthony
authors: A
authors: Lucas
authors: Emilie
authors: E
authors: Dorchies
authors: Mehdi
authors: M
authors: Daoudi
authors: Sophie
authors: S
authors: Lestavel
authors: Frank J
authors: FJ
authors: Gonzalez
authors: Matej
authors: M
authors: Oresic
authors: Bertrand
authors: B
authors: Cariou
authors: Folkert
authors: F
authors: Kuipers
authors: Sandrine
authors: S
authors: Caron
authors: Bart
authors: B
authors: Staels
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