title: Clinical relevance of the bile acid receptor TGR5 in metabolism.
abstract: The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus on the translation of preclinical studies into clinically applicable findings. Studies in rodents suggest an important role for Tgr5 in Glp-1 secretion, insulin sensitivity, and energy expenditure. However, evidence of effects on these processes from human studies is less convincing. Ultimately, safe and selective human TGR5 agonists are needed to test the therapeutic potential of TGR5.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: F Samuel
authors.initials: FS
authors.lastname: van Nierop
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Matthijs J
authors.initials: MJ
authors.lastname: Scheltema
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Eggink
authors.affiliation: Department of Biochemistry, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Thijs W
authors.initials: TW
authors.lastname: Pols
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: David P
authors.initials: DP
authors.lastname: Sonne
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Hellerup, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands. Electronic address: m.r.soeters@amc.nl.
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Soeters
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004734:Energy Metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; C473772:GPBAR1 protein, human; C513561:Gpbar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1; D005947:Glucose