Kusakabe, Y. | bioRxiv Science

bioRxiv2026

Circadian Regulation of Taste Sensitivity in Human and Rat Active Periods

Most organisms exhibit endogenous 24-h rhythms that align physiology and behavior with the time of day; however, whether taste sensitivity oscillates in a circadian manner remains unclear, limiting our understanding of its role in feeding behavior. Here, we show that sensitivity to sweet and bitter tastes exhibits circadian modulation, peaking during the active period: daytime in humans and the dark phase in nocturnal rats. In humans, the rhythmicity of sweet taste was evident in detection but not recognition thresholds, indicating circadian modulation at the level of primary sensory processing rather than higher-order cognitive processes. In rats, increased sensitivity during the dark phase was accompanied by upregulation of taste-related genes in type II taste cells in tongue. These findings provide evidences that circadian regulation of taste sensitivity is conserved across species and appears to operate predominantly at the peripheral level. This mechanism may have evolved to optimize energy intake while minimizing exposure to dietary toxins, potentially contributing to survival and continuing to influence modern eating behavior through circadian-sensory-nutritional interactions.

physiology↗

bioRxiv2019

Differential scanning fluorimetric analysis of the amino-acid binding to taste receptor using a model receptor protein, the ligand-binding domain of fish T1r2a/T1r3

Taste receptor type 1 (T1r) is responsible for the perception of essential nutrients, such as sugars and amino acids, and evoking sweet and umami (savory) taste sensations. T1r receptors recognize many of the taste substances at their extracellular ligand-binding domains (LBDs). In order to detect a wide array of taste substances in the environment, T1r receptors often possess broad ligand specificities. However, the entire ranges of chemical spaces and their binding characteristics to any T1rLBDs have not been extensively analyzed. In this study, we exploited the differential scanning fluorimetry (DSF) to medaka T1r2a/T1r3LBD, a current sole T1rLBD heterodimer amenable for recombinant preparation, and analyzed their thermal stabilization by adding various amino acids. The assay showed that the agonist amino acids induced thermal stabilization and shifted the melting temperatures (Tm) of the protein. An agreement between the DSF results and the previous biophysical assay was observed, suggesting that DSF can detect ligand binding at the orthosteric-binding site in T1r2a/T1r3LBD. The assay further demonstrated that most of the tested L-amino acids, but no D-amino acid, induced Tm shifts of T1r2a/T1r3LBD, indicating the broad L-amino acid specificities of the proteins probably with several different manners of recognition. The Tm shifts by each amino acid also showed a fair correlation with the responses exhibited by the full-length receptor, verifying the broad amino-acid binding profiles at the orthosteric site in LBD observed by DSF.

biochemistry↗