HEPATIC MECHANISM FOR CONTROL OF FOOD INTAKE

描述(改编自申请者摘要)：这是一次续签 对肝脏对喂养的影响给予额外的5年补助。这个 Pi和他的同事们已经完成了对果糖的广泛研究 模拟，2，5-AM。这种药物减少了肝脏中三磷酸腺苷的形成， 信号被传递到大脑，导致开始进食。《少年派》 现在建议完成必要的广泛研究，以证明 一种药物在肝脏中起作用或不起作用，从而影响饮食 另外三种抗代谢药物：哇巴因、乙硫氨酸和巯基乙酸酯。 在相关实验中，将给予标记药物，肝、脑、 对肾脏、附睾部脂肪和肌肉进行摄取分析。 在第二系列拟议的实验中，门静脉和肝内 2，5-AM的输注将与迷走神经的肝支进行比较 不是完整的就是切好的。其目的是确定2，5-AM诱导的进食是否 由肝脏信号在迷走神经或迷走神经的几个分支中传播引起 其他的在肝床的几个器官中。第三系列实验 将使用两种方法，CFOS诱导和局部脑葡萄糖 利用标记的2-脱氧葡萄糖，以确定 下脑干被2，5-AM激活。

DESCRIPTION (Adapted from applicant's abstract): This is a renewal for 5 additional years a grant on the hepatic influences upon feeding. The PI and his colleagues have completed extensive work with the fructose analogue, 2,5-AM. The drug reduces ATP formation in the liver and a signal is relayed to the brain that causes initiation of eating. The PI now proposes to complete the extensive studies necessary to demonstrate that a drug does or does not act in the liver to influence eating with three other antimetabolites: Ouabain, ethionine and mercaptoacetate. In related experiments, labelled drug will be given and the liver, brain, kidneys, epididymal fat and muscle analyzed for uptake. In a second series of proposed experiments, intraportal and intrahepatic infusions of 2,5-AM will be compared with the hepatic branch of the vagus intact or cut. The purpose is to determine if 2,5-AM-elicited eating is caused by hepatic signals travelling in several branches of the vagus or else in several organs in the hepatic bed. A third series of experiments will use two methods, cFOS induction and local cerebral glucose utilization of labelled 2-deoxyglucose, to ascertain which areas of the lower brainstem are activated by 2,5-AM.