Statins and transcriptional regulation: The FXR connection

• Published in: Biochemical and biophysical research communications 2005-08, Vol.334 (2), p.601-605
• Main Authors: Habeos, Ioannis, Ziros, Panos G., Psyrogiannis, Agathoklis, Vagenakis, Apostolos G., Papavassiliou, Athanasios G.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Administration, Oral; Animals; Cell Line; Cells, Cultured; Cricetinae; DNA; DNA binding; DNA-Binding Proteins - metabolism; DRUGS; Farnesoid X receptor; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; GENE REGULATION; GENES; GLUCOSE; HAMSTERS; Hepatocytes - drug effects; Hepatocytes - metabolism; HOMEOSTASIS; HORMONES; Lipoprotein metabolism; LIPOPROTEINS; Liver - drug effects; Liver - metabolism; Male; Mesocricetus; METABOLISM; RECEPTORS; Receptors, Cytoplasmic and Nuclear; RNA; Simvastatin; Simvastatin - pharmacology; Tissue Distribution; Transcription Factors - metabolism; Transcriptional Activation - drug effects; Transcriptional Activation - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.06.129

Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism.