FXR-deficiency confers increased susceptibility to torpor.
The role of the nuclear receptor FXR in adaptive thermogenesis was investigated using FXR-deficient mice. Despite elevated serum bile acid concentrations and increased mRNA expression profiles of thermogenic genes in brown adipose tissue, FXR-deficiency did not alter energy expenditure under basal conditions. However, FXR-deficiency accelerated the fasting-induced entry into torpor in a leptin-dependent manner. FXR-deficient mice were also extremely cold-intolerant. These altered responses may be linked to a more rapid decrease in plasma concentrations of metabolic fuels (glucose, triglycerides) thus impairing uncoupling protein 1-driven thermogenesis. These results identify FXR as a modulator of energy homeostasis.
Cariou
Bertrand
B
Institut Pasteur de Lille, Département d'Athérosclérose, Lille F-59019, France.
Bouchaert
Emmanuel
E
Abdelkarim
Mouaadh
M
Dumont
Julie
J
Caron
Sandrine
S
Fruchart
Jean-Charles
JC
Burcelin
Rémy
R
Kuipers
Folkert
F
Staels
Bart
B
D000064:Acclimatization / Q000235:genetics / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000097:blood; D001833:Body Temperature Regulation / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005260:Female; D006706:Homeostasis; D007035:Hypothermia / Q000235:genetics / Q000503:physiopathology; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D017931:DNA Primers; D004268:DNA-Binding Proteins; D020738:Leptin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated