Sweet taste receptors play roles in artificial sweetener-induced enhanced urine output in mice

Sweet taste receptors in oral and extraoral tissues regulate diverse physiological functions. Lifetime exposure to artificial sweeteners has been associated with increased urine volume, but mechanisms and differential effects among sweeteners are unclear. Using behavioral assays, western blotting, and RT-qPCR in mice, we examined urine excretion and sweet taste receptor expression after exposure to three artificial sweeteners at low (ADI-based) or higher concentrations. High-dose acesulfame potassium (AceK) and saccharin significantly increased urine output, with a positive correlation between urinary K+ concentration and urination volume. In T1R3 knockout mice, AceK-induced changes in urine output were attenuated, indicating involvement of sweet taste signaling. T1R3 gene expression was specifically upregulated in bladder, but not kidney or other tested organs. Our results indicate that extraoral sweet taste receptors, including those in bladder, contribute to enhanced urine output. Long-term exposure effects differed among sweeteners; AceK increased urine output even at very low concentrations.

Shuangfeng Cai, Ningning Xie, Ling Zheng, Quan Li, Siyu Zhang, Qinghua Huang, Wei Luo, Mei Wu, Yidan Wang, Yilun Du, Shao-ping Deng, Lei Cai