Hindbrain integration of adiposity and satiety signals

描述(由申请人提供)：这项建议研究神经回路，它整合了脂肪激素瘦素和肠源性饱腹感信号CCK(CCK)在控制食物摄入方面的输入。现有数据为瘦素减少食物摄入量的假设提供了令人信服的支持，该假说部分是通过增加饱腹感和后脑对胃肠道信号(包括CCK)的反应来实现的。在这里，我们建议识别后脑神经元的特定子集，其对CCK的反应由瘦素刺激。其次，我们将确定瘦素和CCK之间的相互作用是否会随着瘦素水平的生理性变化而发生，这一点在瘦素的药理剂量中得到了明确的证明。最后，我们将确定瘦素是通过尾侧脑干内的直接作用还是通过间接途径(可能涉及前脑的下行投射)调节后脑细胞对CCK的反应。总之，这些研究将有助于阐明体内脂肪储备的变化如何导致对膳食大小的补偿性调整，从而有可能显著提高我们对调节能量平衡的神经回路的理解。

DESCRIPTION (provided by applicant): This proposal investigates the neural circuitry that integrates input from the adiposity hormone, leptin, and the gut-derived satiety signals, cholecystokinin (CCK), in the control of food intake. Available data provides compelling support for the hypothesis that leptin reduces food intake in part by enhancing satiety and hindbrain responses to gastrointestinal signals, including CCK. Here, we propose to identify the specific subset of hindbrain neurons whose responses to CCK are stimulated by leptin. Second, we will determine whether the interaction between leptin and CCK, clearly demonstrated with pharmacological doses of leptin, occurs with physiological changes in leptin levels. Finally, we will determine whether leptin regulates hindbrain cell responsiveness to CCK through a direct action within the caudal brainstem or through an indirect route, perhaps involving a descending projection from the forebrain. Together, these studies will help to clarify how changes in body fat stores lead to compensatory adjustments of meal size and thus have the potential to significantly advance our understanding of the neural circuitry that regulates energy balance.