Leptin as a modulator of sweet taste sensitivities in mice
Leptin as a modulator of sweet taste sensitivities in mice
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DOI：
10.1073/pnas.190066697
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发表时间：
2000-09-26
影响因子：
11.1
通讯作者：
Ninomiya, Y
中科院分区：
文献类型：
--
作者：
Kawai, K;Sugimoto, K;Ninomiya, Y
瘦素通过调节能量消耗、食物摄入量和肥胖，成为一种有效的肥胖抑制因子。肥胖的糖尿病db/db小鼠存在瘦素受体缺陷，表现出增强的神经反应和对甜味刺激的行为偏好。这里，我们展示了瘦素对外周味觉系统的影响。瘦素可抑制周围味觉神经(鼓索和舌咽)对甜味物质(蔗糖和糖精)的反应，而不影响对酸、咸和苦物质的反应。全细胞膜片钳记录舌咽神经支配的环状乳头味觉感受器细胞的活动表明，瘦素激活外向钾电流，导致味觉细胞超极化。瘦素受体受损的db/db小鼠没有表现出这种瘦素抑制。瘦小鼠的味觉组织(环状乳头)表达瘦素受体mRNA，部分味觉细胞表现出对瘦素受体抗体的免疫反应。综上所述，这些观察结果表明，味觉器官是瘦素的外周靶标，瘦素可能是一种甜味调节因子(抑制因子)，可能参与调节食物摄入量。Db/db小鼠这种瘦素抑制系统的缺陷可能会导致它们的外周神经反应增强，并增强对甜味物质的行为偏好。
Leptin acts as a potent inhibitory factor against obesity by regulating energy expenditure, food intake, and adiposity. The obese diabetic db/db mouse, which has defects in leptin receptor, displays enhanced neural responses and elevated behavioral preference to sweet stimuli. Here, we show the effects of leptin on the peripheral taste system. An administration of leptin into lean mice suppressed responses of peripheral taste nerves (chorda tympani and glossopharyngeal) to sweet substances (sucrose and saccharin) without affecting responses to sour, salty, and bitter substances. Whole-cell patch-clamp recordings of activities of taste receptor cells isolated from circumvallate papillae (innervated by the glossopharyngeal nerve) demonstrated that leptin activated outward K+ currents, which resulted in hyperpolarization of taste cells. The db/db mouse with impaired leptin receptors showed no such leptin suppression. Taste tissue (circumvallate papilla) of lean mice expressed leptin-receptor mRNA and some of the taste cells exhibited immunoreactivities to antibodies of the leptin receptor. Taken together, these observations suggest that the taste organ is a peripheral target for leptin, and that leptin may be a sweet-sensing modulator (suppressor) that may take part in regulation of food intake. Defects in this leptin suppression system in db/db mice may lead to their enhanced peripheral neural responses and enhanced behavioral preferences for sweet substances.