Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures
Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures
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DOI：
10.1210/en.2003-0602
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发表时间：
2004-02-01
期刊：
影响因子：
4.8
通讯作者：
Ninomiya, Y
中科院分区：
文献类型：
--
作者：
Shigemura, N;Ohta, R;Ninomiya, Y
瘦素是一种主要通过下丘脑功能性瘦素受体Ob-Rb调节体重稳态的激素。最近，我们提出味觉器官是瘦素的新的外周靶点。瘦素选择性地抑制小鼠味觉细胞对甜味物质的反应，从而可以作为甜味调节剂。本研究通过检测瘦素缺陷型ob/ob、ob-Rb缺陷型db/db小鼠及其正常同窝小鼠味觉细胞Ob-Rb的表达和对甜味物质的行为反应，进一步研究瘦素对味觉系统的作用。RT-PCR分析表明，Ob-Rb在所有供试菌株的味细胞中均有表达。然而，db/db小鼠的RT-PCR产物中含有异常db插入，导致细胞内结构域受损。原位杂交结果表明，正常Ob-Rb mRNA在瘦鼠和ob/ob鼠的味细胞中有杂交信号，而在db/db鼠的味细胞中无杂交信号。两个不同的行为测试，一个使用甜苦混合物作为味觉刺激，另一个条件性味觉厌恶范例，表明在ob/ob和正常同窝小鼠中ip注射瘦素后，对蔗糖和糖精的反应显著降低，但在db/db小鼠中没有。这些结果表明，瘦素抑制行为反应的甜味物质通过其作用于Ob-Rb的味觉细胞。瘦素对味觉的调节可能与食物摄入的调节有关。
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.