title: The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice.
abstract: Intestinal chemosensory signaling pathways involving the gustatory G-protein, gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB), but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Gasthuisberg O&N1, box 701, 3000 Leuven, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Avau
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Gasthuisberg O&N1, box 911, 3000 Leuven, Belgium.
authors.forename: Dries
authors.initials: D
authors.lastname: Bauters
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Gasthuisberg O&N1, box 701, 3000 Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steensels
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Gasthuisberg O&N1, box 701, 3000 Leuven, Belgium.
authors.forename: Laurien
authors.initials: L
authors.lastname: Vancleef
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Gasthuisberg O&N1, box 701, 3000 Leuven, Belgium.
authors.forename: Jorien
authors.initials: J
authors.lastname: Laermans
authors.affiliation: Laboratory of Livestock Physiology, Department of Biosystems, University of Leuven, Kasteelpark Arenberg 30, 3001 Leuven, Belgium.
authors.forename: Jens
authors.initials: J
authors.lastname: Lesuisse
authors.affiliation: Laboratory of Livestock Physiology, Department of Biosystems, University of Leuven, Kasteelpark Arenberg 30, 3001 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Buyse
authors.affiliation: Center for Molecular and Vascular Biology, University of Leuven, Gasthuisberg O&N1, box 911, 3000 Leuven, Belgium.
authors.forename: H Roger
authors.initials: HR
authors.lastname: Lijnen
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Gasthuisberg O&N1, box 701, 3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Gut Peptide Research Lab, University of Leuven, Gasthuisberg O&N1, box 701, 3000 Leuven, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Depoortere
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000473:pathology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013649:Taste; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D000644:Quaternary Ammonium Compounds; D043562:Receptors, G-Protein-Coupled; C560578:Tas2R108 protein, mouse; C000609219:Tas2R135 protein, mouse; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C043414:denatonium; D052216:Glucagon-Like Peptide 1; D011803:Quinine; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins