Shigemura Noriatsu, Ohta Rie, Kusakabe Yuko, Miura Hirohito, Hino Akihiro, Koyano Kiyoshi, Nakashima Kiyohito, Ninomiya Yuzo
Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Endocrinology. 2004 Feb;145(2):839-47. doi: 10.1210/en.2003-0602. Epub 2003 Oct 30.
Leptin is a hormone that regulates body weight homeostasis mainly via the hypothalamic functional leptin receptor Ob-Rb. Recently, we proposed that the taste organ is a new peripheral target for leptin. Leptin selectively inhibits mouse taste cell responses to sweet substances and thereby may act as a sweet taste modulator. The present study further investigated leptin action on the taste system by examining expression of Ob-Rb in taste cells and behavioral responses to sweet substances in leptin-deficient ob/ob, and Ob-Rb-deficient db/db mice and their normal litter mates. RT-PCR analysis showed that Ob-Rb was expressed in taste cells in all strains tested. The db/db mice, however, had a RT-PCR product containing an abnormal db insertion that leads to an impaired shorter intracellular domain. In situ hybridization analysis showed that the hybridization signals for normal Ob-Rb mRNA were detected in taste cells in lean and ob/ob mice but not in db/db mice. Two different behavioral tests, one using sweet-bitter mixtures as taste stimuli and the other a conditioned taste aversion paradigm, demonstrated that responses to sucrose and saccharin were significantly decreased after ip injection of leptin in ob/ob and normal littermates, but not in db/db mice. These results suggest that leptin suppresses behavioral responses to sweet substances through its action on Ob-Rb in taste cells. Such taste modulation by leptin may be involved in regulation for food intake.
瘦素是一种主要通过下丘脑功能性瘦素受体Ob-Rb来调节体重稳态的激素。最近，我们提出味觉器官是瘦素新的外周靶点。瘦素可选择性抑制小鼠味觉细胞对甜味物质的反应，因此可能作为一种甜味调节剂发挥作用。本研究通过检测Ob-Rb在味觉细胞中的表达以及瘦素缺乏的ob/ob小鼠、Ob-Rb缺乏的db/db小鼠及其正常同窝仔鼠对甜味物质的行为反应，进一步研究了瘦素对味觉系统的作用。逆转录聚合酶链反应（RT-PCR）分析表明，在所检测的所有品系的味觉细胞中均有Ob-Rb表达。然而，db/db小鼠的RT-PCR产物含有异常的db插入片段，导致细胞内结构域缩短且功能受损。原位杂交分析显示，在瘦小鼠和ob/ob小鼠的味觉细胞中检测到正常Ob-Rb mRNA的杂交信号，但在db/db小鼠中未检测到。两项不同的行为测试，一项使用甜-苦混合物作为味觉刺激，另一项是条件性味觉厌恶范式，结果表明，腹腔注射瘦素后，ob/ob小鼠及其正常同窝仔鼠对蔗糖和糖精的反应显著降低，但db/db小鼠没有。这些结果表明，瘦素通过作用于味觉细胞中的Ob-Rb来抑制对甜味物质的行为反应。瘦素的这种味觉调节作用可能参与食物摄入的调节。
