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.
Subject(s)
Brain Stem/metabolism , Duodenum/metabolism , Hypothalamus/metabolism , Obesity/genetics , Receptors, G-Protein-Coupled/genetics , Animals , Brain Stem/pathology , Duodenum/pathology , Energy Metabolism/genetics , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Gene Expression Regulation , Glucose/metabolism , Glucose/pharmacology , Homeostasis/genetics , Hypothalamus/pathology , Leptin/metabolism , Leptin/pharmacology , Mice , Mice, Inbred C57BL , Mice, Obese , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Obesity/metabolism , Obesity/pathology , Primary Cell Culture , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptors, G-Protein-Coupled/metabolism , Signal Transduction , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism , Taste/genetics , Taste Buds/metabolism , Taste Buds/pathologyABSTRACT
BACKGROUND: As a result of the very efficient capture of allergens by IgE that focuses to CD23 on B cells or FcepsilonRI on dendritic cells, allergen-specific T cells can be activated after exposure to very low levels of allergens. This IgE-mediated allergen presentation is 100- to 1,000-fold more efficient than fluid phase endocytosis. The aim of the present study was to determine whether humanized anti-IgE mAb Hu-901 can prevent the activation of allergen-specific T cells by inhibiting IgE-mediated allergen presentation. METHODS: A house dust mite major allergen Der p 1-specific T cell line was generated from an allergic asthma patient, and a model was set up to show IgE-facilitated allergen presentation via CD23 on EBV-transformed B cells. In addition, experiments were performed by FACS analysis, detecting the presence of IgE-allergen complexes bound to EBV-B cells by polyclonal FITC-labeled anti-IgE antisera. RESULTS: The anti-IgE mAb Hu-901 inhibited proliferation of allergen-specific T cells at low allergen concentrations. Inhibition was dose-dependent. This effect could be explained by Hu-901 inhibition of binding of allergen-IgE complexes to CD23 expressed on EBV-transformed B lymphocytes. CONCLUSIONS: These data clearly indicate that anti-IgE antibodies for the treatment of allergy exert their effect not only by inhibiting mast cell/basophil degranulation, but also by preventing T cell activation, which possibly explains the effect of anti-IgE treatment on late-phase reactions noted in clinical studies.
