Bile acid signaling to the nucleus: finding new connections in the transcriptional regulation of metabolic pathways.
Recent findings indicate that the function of metabolically relevant genes is finely regulated at the level of gene transcription. Disturbances of these regulatory pathways often lead to metabolic unbalance and to the onset of socially relevant diseases, i.e. diabetes, metabolic syndrome, atherosclerosis and cardiovascular diseases. The ability of lipid metabolites, such as fatty acids and oxysterols, to signal to cells and tissues and to affect gene transcription by activating specific nuclear receptors has been known since several years. Bile acids have been known in the past as cholesterol end products, purely acting as detergents. Only recently new biological properties of bile acids as signaling molecules have been disclosed and appreciated. In this review, we will describe how bile acids can regulate their own synthesis and other metabolic pathways (i.e. glucose metabolism) by modulating gene transcription through multiple mechanisms. These findings also open new perspectives towards the exploitation of bile acid metabolism as a pharmacological target.
De Fabiani
Emma
E
Dipartimento di Scienze Farmacologiche, Facoltà di Farmacia, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
Mitro
Nico
N
Godio
Cristina
C
Gilardi
Federica
F
Caruso
Donatella
D
Crestani
Maurizio
M
D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013261:Sterols / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D000098825:Oxysterol Binding Proteins
D001647:Bile Acids and Salts; D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors; D011987:Receptors, Steroid; D013261:Sterols; D000098825:Oxysterol Binding Proteins