Laboratory of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Peptides. 2013 Sep;47:115-23. doi: 10.1016/j.peptides.2013.07.015. Epub 2013 Jul 26.
Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is effective in inducing weight loss. The exact mechanisms are not fully understood. Reduced appetite and food intake may play important roles. Sweet taste contributes to food palatability, which promotes appetite. Interestingly, GLP-1 and its receptor are expressed in the taste buds of rodents and their interaction has an effect on mediating sweet taste sensitivity. Our aim was to investigate whether sweet taste will be changed after long term treatment with exenatide. The results showed that high-fat diet induced obese rats (HF-C) presented metabolic disorders in food intake, body weight, blood glucose and lipid metabolism compared with long term exenatide treated obese rats (EX) and normal chow fed control rats (NC). Meanwhile, greater preference for sweet taste was observed in HF-C rats but not in EX rats. Compared with NC rats, brain activities induced by sweet taste stimulation were stronger in HF-C rats, however these stronger activities were not found in EX rats. We further found reduced sweet taste receptor T1R3 in circumvallte taste buds of HF-C rats, while GLP-1 was increased. Besides, serum leptin was evaluated in HF-C rats with decreased leptin receptor expressed in taste buds. These changes were not observed in EX rats, which suggest them to be the underlying hormone and molecular mechanisms responsible for alterations in sweet taste of HF-C rats and EX rats. In summary, our results suggest that long term treatment with exenatide could benefit dietary obese rats partially by reversing sweet taste changes.
艾塞那肽，一种胰高血糖素样肽-1（GLP-1）受体激动剂，在诱导体重减轻方面非常有效。其确切机制尚未完全阐明。降低食欲和食物摄入量可能发挥着重要作用。甜味有助于食物的美味，从而促进食欲。有趣的是，GLP-1及其受体在啮齿动物的味蕾中表达，它们的相互作用对调节甜味敏感性有影响。我们的目的是研究长期使用艾塞那肽治疗后甜味是否会发生变化。结果表明，与长期艾塞那肽治疗肥胖大鼠（EX）和正常饮食对照组大鼠（NC）相比，高脂肪饮食诱导肥胖大鼠（HF-C）在食物摄入、体重、血糖和脂质代谢方面表现出代谢紊乱。同时，HF-C 大鼠对甜味的偏好更大，但 EX 大鼠则不然。与 NC 大鼠相比，HF-C 大鼠的甜味刺激引起的大脑活动更强，但在 EX 大鼠中则没有发现这些更强的活动。我们进一步发现 HF-C 大鼠的环层味蕾中的甜味受体 T1R3 减少，而 GLP-1 增加。此外，HF-C 大鼠的血清瘦素水平降低，而味觉中的瘦素受体表达减少。这些变化在 EX 大鼠中未观察到，这表明它们是 HF-C 大鼠和 EX 大鼠甜味变化的潜在激素和分子机制。总之，我们的研究结果表明，长期使用艾塞那肽可能通过逆转甜味变化，使饮食肥胖大鼠受益。
