Potential regulatory role of the farnesoid X receptor in the metabolic syndrome.
Dyslipidemia and gallbladder diseases are two current anomalies observed in patients suffering from the metabolic syndrome and type 2 diabetes. The bile acid-activated nuclear receptor farnesoid X receptor (FXR) controls bile acid as well as lipid metabolism. Recent observations indicate a role for FXR also in carbohydrate metabolism. Hepatic FXR expression is altered in diabetic animal models in vivo and regulated by hormones and nutrients in vitro. At the molecular level, FXR activation modifies the transcriptional activity of different transcription factors controlling gluconeogenesis and lipogenesis, thus affecting in concert bile acid, lipid and carbohydrate metabolism. The present review focuses on recent advances in our understanding of the modulation of carbohydrate metabolism by FXR. These observations raise the intriguing possibility for a modulatory role of this receptor also in the metabolic syndrome.
Duran-Sandoval
Daniel
D
U.R.545 Inserm, Département d'Atherosclerosis, Institut Pasteur de Lille et Faculté de Pharmacie, Université de Lille 2, 1, rue du Professeur-Calmette, BP245, 59019 Lille, France.
Cariou
Bertrand
B
Fruchart
Jean-Charles
JC
Staels
Bart
B
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005346:Fibroblast Growth Factors / Q000502:physiology; D005943:Gluconeogenesis; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000503:physiopathology*; D047493:PPAR alpha / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005346:Fibroblast Growth Factors; D047493:PPAR alpha; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated