HEPATIC MECHANISM FOR CONTROL OF FOOD INTAKE

描述（改编自申请人摘要）：摄食行为部分受吸收后燃料代谢控制。为了让能量代谢影响进食，大脑必须被告知。肝脏监测燃料代谢，并产生信号，大脑用它来控制进食行为。这个项目的总体目标是了解肝脏控制食物摄入的运作。本实验将提供控制摄食行为的肝脏机制的重要信息，从而有助于更全面地了解暴饮暴食、肥胖和厌食症的病因，并制定适当的预防和治疗策略。本项目的两个目标涉及肝脏饥饿信号传递和处理的神经基质。实验将进行：1)定位参与肝脏代谢性饥饿信号传递和加工的神经元；2)确定不同外周代谢饥饿信号在何处被整合以控制摄食行为。该项目的三个目标是解决有关肝脏机制介导葡萄糖和脂肪饱腹感的问题。为了解决这些问题，将进行实验以确定：1)供应肝脏的血管（肝动脉和肝门静脉）中葡萄糖浓度的差异是否产生饱腹感信号；2)迷走神经感觉神经元介导高浓度肝门静脉葡萄糖的饱足效应；3)脂肪的饱腹作用是由于它在肝脏中的代谢。该项目的另一个目的是研究肝脏中哪些类型的细胞是控制摄食行为的肝脏信号的来源。为了解决这个问题，将进行一项实验，以确定代谢饥饿信号是否来自肝细胞。

DESCRIPTION (Adapted From The Applicant's Abstract): Feeding behavior is controlled in part by post-absorptive fuel metabolism. In order for fuel metabolism to affect feeding, the brain must be informed. The liver monitors fuel metabolism and generates signals that the brain uses to control feeding behavior. The overall goal of this project is to understand the operation of this hepatic control of food intake. The experiments proposed in this application will provide important information about hepatic mechanisms that control feeding behavior, and thus will contribute to a fuller understanding of the etiology of overeating, obesity and anorexia, and to the development of appropriate strategies for their prevention and treatment. Two aims of this project pertain to the neural substrate for the transmission and processing of the hepatic hunger signal(s). Experiments will be performed to: 1) locate the neurons involved in the transmission and processing of hepatic metabolic hunger signals; and 2) determine where different peripheral metabolic hunger signals are integrated to control feeding behavior. Three aims of the project address questions concerning the hepatic mechanism that mediates satiety in glucose and fat. To address these issues experiments will be conducted to determine whether: 1) the difference in glucose concentration in the blood vessels supplying the liver (hepatic artery and hepatic portal vein) generates a satiety signal; 2) the sensory neurons in the vagus nerves mediate the satiating effect of high concentrations of hepatic portal vein glucose; and 3) the satiating effect of fat is due to its metabolism in the liver. Another aim of this project pertains to which cell types in the liver are the source of hepatic signals that control feeding behavior. To address this, an experiment will be performed to determine whether a metabolic hunger signal originates from hepatocytes.