FXR: a promising target for the metabolic syndrome?
The metabolic syndrome is an insulin-resistant state that is characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the role of the bile-acid-activated farnesoid X receptor (FXR) in the modulation of the metabolic syndrome. Owing to its regulatory actions in lipid and glucose homeostasis, FXR is a potential pharmacological target. Moreover, the observation that FXR also influences endothelial function and atherosclerosis indicates a regulatory role in the cardiovascular complications that are associated with the metabolic syndrome. The pharmacological activation of FXR leads to a complex response that integrates beneficial actions and potentially undesirable side-effects. Thus, the identification of selective FXR modulators (selective bile acid receptor modulators) is required for the development of compounds that can be used to treat the metabolic syndrome.
Cariou
Bertrand
B
Centre Hospitalier Universitaire Hôtel-Dieu, Nantes 44093, France. bertrand.cariou@univ-nantes.fr
Staels
Bart
B
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D001647:Bile Acids and Salts / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D005947:Glucose; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated