METABOLIC CONTROL OF FEEDING BEHAVIOR

进食行为的代谢控制

• 批准号: 6610679
• 负责人: MARK FRIEDMAN
• 金额: $ 30.49万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6610679
• 关键词: adenosine triphosphate; antimetabolites; behavior prediction; bioenergetics; calcium flux; carbohydrate analog; laboratory rat; liver cells; liver metabolism; mannitol; nuclear magnetic resonance spectroscopy; nutrient intake activity; nutrition related tag; obesity; ouabain; overeating; psychobiology; sodium potassium exchanging ATPase

DESCRIPTION (provided by applicant): Postabsorptive fuel metabolism is an important factor in the control of food intake. Sensors in brain and liver that are sensitive to various metabolic parameters have been implicated in this control. In liver, considerable evidence indicates that changes in energy metabolism produce a stimulus or stimuli that are transduced into a neural signal that carries this metabolic information to the central nervous system for use in controlling food intake. In particular, changes in hepatic ATP content, or some closely related change in liver energy status, generate signals that initiate or terminate feeding behavior under various conditions, such as fasting-refeeding, type I diabetes, and treatment with metabolic inhibitors. Recent studies in this laboratory have revealed that three different animal models of obesity (genetic, dietary and neurological) show reduced hepatic energy status, suggesting that changes in liver energy status are also involved in overeating and the development of obesity. The overall goal of this project is to assess whether and how altered hepatic energy metabolism is a contributing cause of hyperphagia (overeating) that leads to obesity. Some rats overeat and become obese when fed a diet high in fat content (obesity-prone), whereas others of the same strain do not (obesity-resistant). The proposed research will use this diet-induced animal model of obesity because it appears most comparable to the obesity commonly seen in humans. We hypothesize that, during the development of obesity, hyperphagia may be driven at least in part by decreased liver energy status, which is secondary to the redirection of fuels into storage and away from oxidative pathways. Overeating could result from a faster decline in hepatic energy status between meals or a slower recovery in hepatic energy status during and after a meal. The project has three specific aims: (1) Determine whether overeating in obesity prone rats is due to an enhanced susceptibility to reductions in liver energy status. (2) Determine whether overeating in obesity prone rats is due to a slow restoration of liver energy status. (3) Determine whether calcium signaling during metabolic stimulus transduction differs in hepatocytes from lean and obese rats.

描述（由申请人提供）：吸收后燃料代谢是控制食物摄入的一个重要因素。大脑和肝脏中对各种代谢参数敏感的传感器与这种控制有关。在肝脏中，大量证据表明，能量代谢的变化会产生一种或多种刺激，这些刺激被转变成神经信号，将该代谢信息传递到中枢神经系统，用于控制食物摄入。特别是，肝脏 ATP 含量的变化，或肝脏能量状态的一些密切相关的变化，会产生在各种条件下启动或终止进食行为的信号，例如禁食-再进食、I 型糖尿病和代谢抑制剂治疗。该实验室最近的研究表明，三种不同的肥胖动物模型（遗传性、饮食性和神经性）显示出肝脏能量状态降低，这表明肝脏能量状态的变化也与暴饮暴食和肥胖的发展有关。该项目的总体目标是评估肝脏能量代谢的改变是否以及如何导致饮食过多（暴饮暴食），从而导致肥胖。一些老鼠在喂食脂肪含量高的饮食时会吃得过多并变得肥胖（易肥胖），而同一品系的其他老鼠却不会（抗肥胖）。拟议的研究将使用这种饮食诱发的肥胖动物模型，因为它看起来与人类常见的肥胖最相似。我们假设，在肥胖的发展过程中，食欲亢进可能至少部分是由肝脏能量状态下降引起的，这是燃料重新定向到储存并远离氧化途径的继发因素。暴饮暴食可能是由于两餐之间肝能量状态下降较快或餐中和餐后肝能量状态恢复较慢所致。该项目有三个具体目标：（1）确定肥胖大鼠的暴饮暴食是否是由于肝脏能量状态降低的易感性增加所致。 (2)确定肥胖大鼠的暴饮暴食是否是由于肝脏能量状态恢复缓慢所致。 (3) 确定瘦大鼠和肥胖大鼠肝细胞中代谢刺激转导过程中的钙信号传导是否不同。