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. Taste perception is an important aspect in the control of food intake. Taste is mainly sensed by taste receptor containing cells located in the taste buds distributed in the different gustatory epitheliums in the tongue, palate, larynx and epiglottis. The sensing of sweet, umami and bitter taste is mediated by two G protein-coupled taste receptor (GPCTR) families: the T1R family, which is mainly involved in the sensing of sweet and umami taste-like signalling molecules and the T2R family, involved in the sensing of bitter taste-like signalling molecules 1 . The T1R family consists of three different GPCTRs that generate at least two heterodimeric receptors: T1R1+T1R3 associated with umami taste sensing and T1R2+T1R3 associated with sweet taste sensing 1,2 . In mice the T2R family consists of at least 36 distinct taste receptor members, which individually sense bitter taste like molecules 3 . The human T2R16 selectively recognizes β-glucopyranosides 4 , while the human T2R38 recognizes phenylthiocarbamide (PTC) 5 . The functional importance of the latter two human receptors was demonstrated by the finding that overexpression of either receptor in mice increases food avoidance 6 . Although the T1R and T2R receptor families drive different taste perceptions, they share similar downstream G protein-coupled signalling pathways. In particular, the taste specific α-subunit of the G protein α-gustducin (αGust) is coupled to both receptor families and has been described as critical for sweet and bitter taste responses 7 . Nevertheless, αGust knockout animals still preserve a moderate sensitivity to some bitter compounds and to sweet compounds in higher mM concentration
