Bile acids and the membrane bile acid receptor TGR5--connecting nutrition and metabolism.
A multitude of endocrine, neural, and metabolic signaling pathways are activated upon food intake to coordinate the effective use of the available energy. Bile acids (BAs) are released from the gallbladder after each meal and subsequently facilitate the digestion of nutrients. Since concentrations of BAs increase postprandially in the serum, they are also signals of food availability that bridge nutrition with metabolism. Both nuclear and membrane receptors mediate BA signaling. Whereas the nuclear receptor farnesoid X receptor mainly affects enterohepatic lipid homeostasis, the G protein-coupled receptor TGR5 stimulates glucagon-like protein 1 production in enteroendocrine cells and activates thyroid hormone in brown adipose tissue and muscle, through the stimulation of type 2 iodothyronine deiodinase (D2). Through its insulinotropic effects, TGR5 may improve glucose homeostasis; through the activation of D2, it will stimulate energy expenditure and protect against the onset of obesity. These properties position TGR5 as an attractive and "drugable" target in our fight against the metabolic syndrome.
Thomas
Charles
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP, Illkirch, France.
Auwerx
Johan
J
Schoonjans
Kristina
K
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004734:Energy Metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D001647:Bile Acids and Salts; D052216:Glucagon-Like Peptide 1; D006360:Heat-Shock Proteins; D007453:Iodide Peroxidase; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D043562:Receptors, G-Protein-Coupled; D013963:Thyroid Hormones; D015534:Trans-Activators; D014157:Transcription Factors; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C473772:GPBAR1 protein, human; C513561:Gpbar1 protein, mouse; C486497:PPARGC1A protein, human; C485290:Ppargc1a protein, mouse