NEURAL SUBSTRATES OF METABOLIC CONTROLS OF INGESTION

通常认为，新陈代谢起源的信号有助于 控制食物摄入量。食物摄入量受变量控制的证据 在特定营养素的可获得性或利用率方面已经得出 来自使用特定代谢途径抑制剂的研究。例如, 现在已经知道，抑制葡萄糖代谢和在 适当的情况下，脂肪酸代谢，增加食物摄入量。 然而，尽管有用于治疗的药理工具 阻止葡萄糖和脂肪代谢，精确的解剖底物和 降低底物代谢的神经行为机制 食物摄入量的增加尚不清楚。年提出的一系列实验 本应用程序将检查中央和 检测特定代谢的外周神经底物 开始进食的刺激物。特别是，这些实验 将重点放在尾侧脑干和迷走神经的肝支 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摄食。 使用路径追踪技术的解剖学研究(银染和 辣根过氧化物酶)和对受损大鼠的行为学研究正在计划中 以获得有关神经通路的更多信息 这些喂食的控制。此外，存在和本土化的 底物动员受体对还原脂肪酸的响应 将对氧化进行调查。第二组实验调查了 糖脂代谢在食物摄入量控制中的相互作用 使用正常大鼠和受损大鼠的行为研究，其中 其中一个控制物的神经基质已经被摧毁。最后， 特异性药物对血糖和脂肪的阻断作用 酸在日粮中大量营养素自选中的应用等 将调查味觉对特定常量营养素的反应。 正常动物和有病变诱发缺陷的动物在对照组中 通过葡萄糖化作用和减少脂肪酸氧化来减少食物摄入量 学习。这些研究应该能更好地理解 代谢刺激参与控制两者的机制 正常和不正常的进食行为。

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.