Research in molecular mechanisms of suppression of sweet responses by anti-obesity factor leptin in taste cells.

瘦素是一种由脂肪组织释放的激素，它能抑制食物摄入，增加能量消耗。我们发现瘦素作为小鼠甜味敏感性调节剂的一种新功能。在瘦正常小鼠中，腹腔注射重组瘦素后，味觉神经对甜味刺激的反应被选择性地抑制，这取决于血浆瘦素水平。膜片钳研究表明，细胞外瘦素增强了对甜味敏感的味觉细胞的K^+电流，从而导致膜超极化和甜味剂诱导的去极化减少。RT-PCR和原位杂交分析证实，长形功能性瘦素受体（Ob-Rb） mRNA在瘦小鼠味觉组织和细胞中有特异性表达。具有Ob-Rb缺陷的遗传性糖尿病db/db小鼠，即使使用高剂量的瘦素，也没有表现出对甜味剂的味觉神经反应的抑制，也没有增加味觉细胞的全细胞K^+传导。这些结果表明，Ob-Rb在瘦小鼠的甜味反应味觉细胞中特异性表达，瘦素通过激活K^+通道抑制甜味诱导的去极化，导致甜味纤维冲动减少。这也表明db/db小鼠对甜味反应的增强可能是由于缺乏瘦素的抑制调节。

Leptin, a hormone released from the adipose tissue, inhibits food intake and increases energy expenditure. We have found a novel function of leptin as a modulator of sweet taste sensitivity in mice. In the lean normal mice, the gustatory nerve responses to sweet stimuli were selectively suppressed depending on plasma leptin level after an intraperitoneal injection of recombinant leptin. Patch-clamp studies using isolated taste cells of lean mice showed that extracellular leptin enhanced K^+ currents of sweet-responsive taste cells, which led to membrane hyperpolarization and a reduction of sweetener-induced depolarization. RT-PCR and in situ hybridization analyzes demonstrated specific expression of mRNA of the long-form functional leptin receptor (Ob-Rb) in taste tissue and cells of lean mice. The genetically diabetic db/db mice, which have defects in Ob-Rb, demonstrated neither a suppression of gustatory neural responses to sweeteners nor an increment of whole-cell K^+ conductance of taste cells even with high doses of leptin. These results suggest that Ob-Rb is specifically expressed in sweet-responsive taste cells of lean mice and that leptin suppresses sweetener-induced depolarization via activation of K^+ channels, leading to a decrease in impulses of sweet-best fibers. It is also suggested that the enhanced sweet responses of db/db mice may result from the lack of inhibitory modulation by leptin.