Endocrine functions of bile acids.
Bile acids (BAs), a group of structurally diverse molecules that are primarily synthesized in the liver from cholesterol, are the chief components of bile. Besides their well-established roles in dietary lipid absorption and cholesterol homeostasis, it has recently emerged that BAs are also signaling molecules, with systemic endocrine functions. BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor TGR5, and activate nuclear hormone receptors such as farnesoid X receptor alpha. Through activation of these diverse signaling pathways, BAs can regulate their own enterohepatic circulation, but also triglyceride, cholesterol, energy, and glucose homeostasis. Thus, BA-controlled signaling pathways are promising novel drug targets to treat common metabolic diseases, such as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.
Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Sander M
SM
Houten
Mitsuhiro
M
Watanabe
Johan
J
Auwerx
D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004703:Endocrine System / Q000502:physiology*; D004734:Energy Metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002784:Cholesterol; D004268:DNA-Binding Proteins; D005947:Glucose; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C473772:GPBAR1 protein, human