Taste receptor gene expression is associated with decreased eGFR in patients with diabetes.

Dysgeusia is not only associated with zinc deficiency but also with certain drugs or diseases, including diabetes and renal failure. It often lowers the patient's quality of life and hinders access to proper nutrition. The underlying mechanism is unclear and there is a lack of awareness among patients. Here, we focused on lingual taste receptor gene expression in diabetes and elucidated the relationship between taste receptor gene expression and renal function. Forty-seven patients with diabetes and 10 healthy subjects (control group) were enrolled. Lingual foliate papillae were scraped and the derived cDNA was quantified by real-time polymerase chain reaction. Dysgeusia was assessed using SALSAVE?. All statistical analyses were performed using JMP? software 13. The expression of T1R1 and T1R2 was significantly upregulated in type 2 diabetes patients as compared with that in healthy subjects (P<0.01) but did not change in type 1 diabetes patients. T1R3 expression positively correlated and Scnn1 expression negatively correlated with estimated glomerular filtration rate, suggesting that altered taste receptor gene expression could reflect impaired renal function. Thus, alterations in T1R3 and Scnn1 expression in diabetes correlated with renal function. Taste receptor gene expression dysregulation could indicate dysgeusia associated with impaired renal function in patients with diabetes. J. Med. Invest. 69 : 120-126, February, 2022.

Development of a screening system for agents that modulate taste receptor expression with the CRISPR-Cas9 system in medaka.

Taste recognition mediated by taste receptors is critical for the survival of animals in nature and is an important determinant of nutritional status and quality of life in humans. However, many factors including aging, diabetes, zinc deficiency, infection with influenza or cold viruses, and chemotherapy can trigger dysgeusia, for which a standard treatment has not been established. We here established an engineered strain of medaka (Oryzias latipes) that expresses green fluorescent protein (GFP) from the endogenous taste 1 receptor 3 (T1R3) gene locus with the use of the CRISPR-Cas9 system. This T1R3-GFP knock-in (KI) strain allows direct visualization of expression from this locus by monitoring of GFP fluorescence. The pattern of GFP expression in the T1R3-GFP KI fish thus mimicked that of endogenous T1R3 gene expression. Furthermore, exposure of T1R3-GFP KI medaka to water containing monosodium glutamate or the anticancer agent 5-fluorouracil resulted in an increase or decrease, respectively, in GFP fluorescence intensity, effects that also recapitulated those on T1R3 mRNA abundance. Finally, screening for agents that affect GFP fluorescence intensity in T1R3-GFP KI medaka identified tryptophan as an amino acid that increases T1R3 gene expression. The establishment of this screening system for taste receptor expression in medaka provides a new tool for the development of potential therapeutic agents for dysgeusia.

Dietary supplementation with monosodium glutamate with dietary balance such as protein, salt and sugar intake with increasing T1R3 taste receptor gene expression in healthy females.

We previously showed that chemotherapy-induced dysgeusia was associated with lingual taste receptor gene expression, and monosodium glutamate (MSG) improved dysgeusia by upregulating taste 1 receptor 3(T1R3) gene expression. In recent years, decreased taste sensitivity has also been reported in some young people, and these are partly due to their disordered eating habits. From these background, we investigated the effects of MSG supplementation on taste receptor expression and dietary intake in healthy females. Fifteen young healthy volunteers were enrolled for the present crossover study and divided in two groups (dietary supplementation with MSG at 2.7 g / day or 0.27 g / day). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative PCR analysis. Food intake was assessed by food frequency questionnaire (FFQg), and body composition was measured using Omron HBF-701. T1R3 expression levels in the tongue and taste sensitivity increased significantly in participants who consumed <10 g of MSG daily, whereas no alteration was observed in participants who consumed >10 g of MSG daily. Furthermore, protein, fat, and carbohydrate (PFC) balance and salt and sugar intake improved by MSG supplementation. In conclusion, MSG supplementation increased T1R3 expression in the tongue and improved dietary balance. J. Med. Invest. 68 : 315-320, August, 2021.

Dietary Supplementation with Monosodium Glutamate Suppresses Chemotherapy-Induced Downregulation of the T1R3 Taste Receptor Subunit in Head and Neck Cancer Patients.

(Background) We investigated the effect of dietary supplementation with monosodium glutamate (MSG) on chemotherapy-induced downregulation of the T1R3 taste receptor subunit expression in the tongue of patients with advanced head and neck cancer. (Methods) Patients undergoing two rounds of chemoradiotherapy were randomly allocated to a control or intervention group (dietary supplementation with MSG at 2.7 g/day during the second round of chemotherapy). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative polymerase chain reaction analysis. Dysgeusia was assessed with a visual analog scale and daily energy intake was evaluated. (Results) T1R3 expression levels in the tongue, taste sensitivity, and daily energy intake were significantly reduced after the first round of chemotherapy compared with before treatment. Furthermore, these parameters significantly decreased after the second round of chemotherapy, but the extent of decrease was significantly attenuated in the MSG group compared with the control group. (Conclusions) MSG supplementation suppresses chemotherapy-induced dysgeusia, possibly due to the inhibition of the T1R3-containing taste receptor downregulation in the tongue, thereby increasing energy intake in patients with advanced head and neck cancer.