NEURAL SUBSTRATES OF METABOLIC CONTROLS OF INGESTION

通常认为，代谢来源的信号有助于 控制食物摄入量。 食物摄入量受变量控制的证据 在特定营养素的可用性或利用率方面， 使用特定代谢途径抑制剂的研究。 例如，在一个示例中， 现在已知抑制葡萄糖代谢， 适当的情况下，脂肪酸代谢，增加食物的摄入量。 然而，尽管有药理学工具， 阻止葡萄糖和脂肪代谢，精确的解剖基质， 降低底物代谢的神经行为机制 增加食物摄入量是未知的。 一系列的实验提出， 本应用程序将检查中央和 用于检测特定代谢的外周神经基质 开始进食的刺激物。特别是，这些实验 将集中在尾脑干和迷走神经的肝分支 因为这些结构似乎含有化学感受器， 通过减少葡萄糖和脂肪酸氧化来刺激进食。 使用通路追踪技术的解剖学研究（银染和 辣根过氧化物酶）和行为研究的损伤大鼠计划 以获得有关参与的神经通路的额外信息， 控制进食此外， 响应于还原脂肪酸的底物动员受体 将研究氧化。第二组实验研究 在控制食物摄入中葡萄糖和脂肪代谢的相互作用 使用正常大鼠和损伤大鼠的行为研究， 其中一个控制系统的神经基质被破坏了最后 特异性药理学诱导葡萄糖和脂肪酸阻断作用 酸利用对膳食大量营养素的自我选择和对 将研究对特定大量营养素的味觉反应。 正常动物和对照组中具有损伤诱导缺陷的动物 通过葡萄糖减少和减少脂肪酸氧化的食物摄入量将 研究了这些研究应有助于更好地了解 代谢刺激参与控制两者的机制 正常和异常的进食行为。

It is generally assumed that signals of metabolic origin contribute to the control food intake. Evidence that food intake is controlled by variations in the availability or utilization of specific nutrients has been derived from studies using inhibitors of specific metabolic pathways. For example, it is now known that inhibition of glucose metabolism and, under appropriate circumstances, fatty acid metabolism, increase food intake. Nevertheless, despite the availability of pharmacological tools for blocking glucose and fat metabolism, the precise anatomical substrates and the neurobehavioral mechanisms by which reduced substrate metabolism increases food intake are not known. One series of experiments proposed in this application will examine the relative importance of central and peripheral neural substrates for the detection of specific metabolic stimuli for the initiation of feeding. In particular, these experiments will focus on the caudal brainstem and the hepatic branch of the vagus since these structures appear to contain chemoreceptors crucial for stimulation of feeding by decreased glucose and fatty acid oxidation. Anatomical studies using pathway tracing techniques (silver stain and horseradish peroxidase) and behavioral studies of lesioned rats are planned to obtain additional information regarding the neural pathways involved in these controls of feeding. in addition, the existence and localization of receptors for mobilization of substrates in response to reduced fatty acid oxidation will be investigated. A second group of experiments investigates the interaction of glucose and fat metabolism in the control of food intake using behavioral studies of normal rats and lesioned rats in which the neural substrate for one of these controls has been destroyed. Finally, the effect of specific pharmacologically-induced blockade of glucose and fatty acid utilization on self-selection of dietary macronutrients and on gustatory responsiveness to specific macronutrients will be investigated. Both normal animals and animals with lesion-induced deficits in the control of food intake by glucoprivation and reduced fatty acid oxidation will be studied. These studies should provide a better understanding of the mechanisms by which metabolic stimuli participate in the control of both normal and abnormal feeding behavior.