| Tas2r108 mediates ligand-specific bitter sensitivity and modulates longevity and metabolic health in mice |
Su Young Ki1,2 
, In Sun Choi3
, Kyung-Nyun Kim3
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1Department of Pharmacology, Korea University College of Medicine, Seoul, Korea
2BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea
3Department of Physiology and Neuroscience, College of Dentistry, Kangwon National University, Gangneung, Korea |
Correspondence:
Kyung-Nyun Kim, Tel: +82-33-640-2450,
Email: knkim@gwnu.ac.kr
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Received: 30 March 2026 • Revised: 5 June 2026 • Accepted: 15 June 2026 |
| Abstract |
Purpose
This study aims to elucidate the physiological functions of the type 2 taste receptor 108 (Tas2r108), highly expressed in the tongue and exocrine tissues, focusing on its role in bitter taste perception, metabolic homeostasis, and longevity.
Materials and Methods
To identify specific ligands, calcium imaging was performed using CHO-K1 cells transfected with Tas2r108 and Gα16gust44. For in vivo functional analysis, a Tas2r108 knock-out (Tas2r108-/-) mouse model was generated using CRISPR/Cas9. Sensory sensitivity was evaluated through two-bottle preference tests, and long-term physiological monitoring assessed body weight, blood pressure, glucose levels, and plasma leptin concentrations.
Results
In vitro assays identified cycloheximide as a primary and potent ligand for Tas2r108 compared to denatonium. In behavioral tests, Tas2r108-/- mice showed a significant reduction in bitter sensitivity to cycloheximide, demonstrating this receptor's essential role in detecting specific bitter ligands. Long-term monitoring revealed that Tas2r108 deficiency significantly extends the average lifespan of mice. While no differences were observed in blood pressure, glucose, or total food intake, Tas2r108-/- mice exhibited greater weight gain during adulthood. Notably, plasma leptin levels were higher in the Tas2r108-/- group, correlating with this period of significant weight gain.
Conclusion
These findings demonstrate that Tas2r108 plays a dual role in mediating ligand-specific bitter taste detection and regulating metabolic health and longevity. The results suggest that Tas2r108 may modulate systemic homeostasis through the leptin signaling pathway, identifying it as a potential target for research into aging and metabolic regulation. |
| Key Words:
Taste; Cycloheximide; Leptin |
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