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.
Houten
Sander M
SM
Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Watanabe
Mitsuhiro
M
Auwerx
Johan
J
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