Abstract
Chemosensory receptors are expressed primarily in sensory organs, but their expression elsewhere can permit ligand detection in other contexts that contribute to survival. The ability of sweet taste receptors to detect natural sugars, sugar alcohols, and artificial sweeteners suggests sweet taste receptors are involved in metabolic regulation in both peripheral organs and in the central nervous system. Our limited knowledge of sweet taste receptor expression in the brain, however, has made it difficult to assess their contribution to metabolic regulation. We, therefore, decided to profile the expression pattern of T1R2, a subunit specific to the sweet taste receptor complex, at the whole-brain level. Using T1r2-Cre knock-in mice, we visualized the overall distribution of Cre-labeled cells in the brain. T1r2-Cre is expressed not only in various populations of neurons, but also in glial populations in the circumventricular organs and in vascular structures in the cortex, thalamus, and striatum. Using immunohistochemistry, we found that T1r2 is expressed in hypothalamic neurons expressing neuropeptide Y and proopiomelanocortin in arcuate nucleus. It is also co-expressed with a canonical taste signaling molecule in perivascular cells of the median eminence. Our findings indicate that sweet taste receptors have unidentified functions in the brain and suggest that they may be a novel therapeutic target in the central nervous system.
Highlights
The principal function of chemosensory receptors in the sensory organs is the detection of exogenous chemicals (Yarmolinsky et al, 2009; Chaudhari and Roper, 2010; Liman et al, 2014)
We have described the comprehensive distribution of T1R2 across the whole brain using genetically engineered
We found that T1r2expressing cells are distributed widely throughout the brain but especially concentrated near the ventricles
Summary
The principal function of chemosensory receptors in the sensory organs is the detection of exogenous chemicals (Yarmolinsky et al, 2009; Chaudhari and Roper, 2010; Liman et al, 2014). Chemosensory receptors are expressed in other organs and tissues where they play unexpected physiological roles responding to their cognate ligands (Calvo and Egan, 2015). In addition to defensive roles like this, the extraoral expression patterns of taste receptors often hint at the roles they play in the regulation of metabolism and physiology. In addition to their expression in taste buds, the subunits of the sweet taste receptor complex—T1R2 and T1R3—are expressed in the intestine (Howitt et al, 2020), pancreas (Nakagawa et al, 2009; Kyriazis et al, 2012), brain (Ren et al, 2009; Kohno et al, 2016), and testes (Mosinger et al, 2013). Sweet taste receptors can function as detectors of internal body state
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