title: Impact of obesity on taste receptor expression in extra-oral tissues: emphasis on hypothalamus and brainstem.
abstract: Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the α-subunits of the associated signalling complex (αGustducin, Gα14 and αTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and α-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Gα14, αTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Gα14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.|Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Herrera Moro Chao
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: C
authors.initials: C
authors.lastname: Argmann
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.|Department of Biochemistry, Leiden Institute of Chemistry, Leiden, 2333 CC, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Van Eijk
authors.affiliation: Department of Biochemistry, Leiden Institute of Chemistry, Leiden, 2333 CC, The Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Boot
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Ottenhoff
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Van Roomen
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Foppen
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: J E
authors.initials: JE
authors.lastname: Siljee
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
authors.forename: U A
authors.initials: UA
authors.lastname: Unmehopa
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.|Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, 1105 BA, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.|Department of Biochemistry, Leiden Institute of Chemistry, Leiden, 2333 CC, The Netherlands.
authors.forename: J M F G
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006706:Homeostasis / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D013649:Taste / Q000235:genetics; D013650:Taste Buds / Q000378:metabolism / Q000473:pathology; D000098706:Taste Receptors, Type 2
chemical_list: C532882:Galpha14 protein, mouse; D020738:Leptin; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; C431926:taste receptors, type 1; D000098706:Taste Receptors, Type 2; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005947:Glucose