FXR-deficiency confers increased susceptibility to torpor

Cariou, Bertrand; Bouchaert, Emmanuel; Abdelkarim, Mouaadh; Dumont, Julie; Caron, Sandrine; Fruchart, Jean-Charles; Burcelin, Rémy; Kuipers, Folkert; Staels, Bart

doi:10.1016/j.febslet.2007.09.064

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Volume 581, Issue 27 , Pages 5191-5198, 13 November 2007

FXR-deficiency confers increased susceptibility to torpor

Edited by Robert Barouki

Bertrand Cariou
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
- Present address: Clinique d’Endocrinologie, Maladies Métaboliques and Nutrition, CHU Hôtel-Dieu, Nantes 44000, France.
Emmanuel Bouchaert
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
Mouaadh Abdelkarim
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
Julie Dumont
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
Sandrine Caron
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
Jean-Charles Fruchart
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
Rémy Burcelin
- Institute of Molecular Medicine, Inserm U858, IFR31, Université Paul Sabatier, Hôpital Rangueil, BP 84225, 31432 Toulouse Cedex 4, France
Folkert Kuipers
- Center for Liver, Digestive and Metabolic Diseases, Laboratory of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands
Bart Staels
- Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France
- Inserm U545, Lille F-59019, France
- Université de Lille 2, Faculté de Pharmacie, Faculté de Médecine, Lille F-59006, France
- Corresponding author. Address: Institut Pasteur de Lille, Département d’Athérosclérose, Lille F-59019, France. Fax: +33 3 20 87 71 98.

Received 28 August 2007; received in revised form 27 September 2007; accepted 30 September 2007. published online 12 October 2007.

Abstract

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.

Keywords: Thermogenesis, Fasting, Cold-exposure, Nuclear receptor