METABOLIC CONTROL OF FEEDING BEHAVIOR

这是一项额外五年支持的请求， 涉及肝脏代谢亚细胞变化的实验以及如何 它们影响大鼠进食的开始。法庭先前出示的证据 研究人员建议，当食物摄入开始后， 在施用代谢抑制剂2，5-AM的情况下，存在几种 在肝细胞中可能有因果关系。更 具体来说，几种类型的实验结果已经趋于一致 强烈暗示肝脏是2，5-AM的靶点， 其他实验表明，一个关键因素（或 至少密切相关）是ATP的量减少， 肝细胞拟议的实验将把分析带到一个更 通过评估结合或游离细胞ATP是否 更多的是与饮食相关，然后确定是否减少 当通过其他方式诱导时，关键ATP池会引起就座;将确定 其他被认为通过肝脏引起进食的药物（例如，甲基 palmoxirate）与类似的肝细胞变化相关;将评估 吃东西的信号与大脑功能有关的假说 肝细胞钠泵;并将确定肝细胞 钙池是一种产生信号的手段， 肝细胞到其他细胞和CNS上。

This is a request for five additional years support to carry out experiments involving metabolic subcellular changes in the liver and how they influence the onset of meals in rats. Prior evidence produced by the investigator suggests that when food intake is initiated after the administration of the metabolic inhibitor, 2, 5-AM, there are several correlates in hepatocytes that may well have a causal role. More specifically, the results of several types of experiments have converged to strongly implicate that the liver is the target for 2, 5-AMs or exigenicaction; and other experiments have indicated that a key factor (or at least close correlate) is a reduction in the amount of ATP in hepatocytes. Proposed experiments will take the analysis to a more reductionistic level by assessing whether bound or free cellular ATP is more correlated with eating and by then determining if a reduction in the key ATP pool elicit seating when induced by other means; will determine if other drugs thought to elicit eating via the liver (e.g., methyl palmoxirate) are associated with similar hepatocyte changes; will assess the hypothesis that the signal to eat is associated with functioning of the hepatocyte sodium pump; and will determine if changes in hepatocyte calcium pools are a means for generating a signal that could pass from hepatocytes to other cells and on the CNS.