METABOLIC CONTROL OF FEEDING BEHAVIOR

进食行为的代谢控制

• 批准号: 6857093
• 负责人: MARK FRIEDMAN
• 金额: $ 31.26万
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6857093
• 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量的重要因素。对大脑和肝脏中对各种代谢参数敏感的传感器已与该对照有关。在肝脏中，大量证据表明，能量代谢的变化会产生刺激或刺激，这些刺激或刺激被引发到神经信号中，该神经信号将这些代谢信息带到中枢神经系统中，以用于控制食物摄入量。特别是，肝ATP含量的变化或肝脏能量状况的某些密切相关的变化会产生信号，这些信号在各种条件下启动或终止喂养行为，例如禁食喂养，I型糖尿病以及对代谢抑制剂的治疗。该实验室的最新研究表明，肥胖的三种不同动物模型（遗传，饮食和神经系统）显示肝能量状况降低，表明肝脏能量状况的变化也参与暴饮暴食和肥胖的发展。该项目的总体目标是评估肝能量代谢是否以及如何改变导致肥胖症的脾气暴躁（暴饮暴食）的原因。一些大鼠吃得过高时，当饮食中的脂肪含量高（容易肥胖）时变得肥胖，而其他菌株的饮食则不会（耐肥胖症）。拟议的研究将使用这种饮食引起的肥胖动物模型，因为它似乎与人类常见的肥胖症最可比。我们假设，在肥胖的发展过程中，超晶状体可能至少部分是由于肝脏能量状态降低而驱动的，这是将燃料重定向储存并远离氧化途径的继发的。暴饮暴食可能是由于饭菜之间肝脏能量状况的降低或进餐期间和之后的肝脏能量状况的恢复较慢而导致的。该项目具有三个特定的目的：（1）确定肥胖大鼠暴饮暴食是否是由于对肝脏能量状况降低的敏感性增强所致。 （2）确定肥胖大鼠暴饮暴食是否是由于肝脏能量状况缓慢恢复。 （3）确定代谢刺激转导期间的钙信号传导是否在瘦大鼠和肥胖大鼠的肝细胞中有所不同。

项目成果

Temporal relationships between eating behavior and liver adenine nucleotides in rats treated with 2,5-AM.

用 2,5-AM 治疗的大鼠饮食行为与肝脏腺嘌呤核苷酸之间的时间关系。

• DOI: 10.1152/ajpregu.1998.274.3.r610
• 发表时间: 1998
• 期刊: The American journal of physiology
• 作者: Koch,JE;Ji,H;Osbakken,MD;Friedman,MI
• 通讯作者: Friedman,MI

Interactions of dietary fat and 2,5-anhydro-D-mannitol on energy metabolism in isolated rat hepatocytes.

膳食脂肪和 2,5-脱水-D-甘露醇对离体大鼠肝细胞能量代谢的相互作用。

• DOI: 10.1152/ajpregu.00159.2001
• 发表时间: 2002
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Ji,Hong;Graczyk-Milbrandt,Grazyna;Osbakken,MaryD;Friedman,MarkI
• 通讯作者: Friedman,MarkI

2,5-Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger stimulus?

2,5-脱水-D-甘露醇增加肝细胞钠：肝脏饥饿刺激的转导？

• DOI: 10.1016/s0167-4889(03)00098-3
• 发表时间: 2003
• 期刊: Biochimica et biophysica acta
• 作者: Friedman,MarkI;Graczyk-Millbrandt,Grazyna;Ji,Hong;Rawson,NancyE;Osbakken,MaryD
• 通讯作者: Osbakken,MaryD

Metabolic inhibitors synergistically decrease hepatic energy status and increase food intake.

代谢抑制剂可协同降低肝脏能量状态并增加食物摄入量。

• DOI: 10.1152/ajpregu.2000.278.6.r1579
• 发表时间: 2000
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Ji,H;Graczyk-Milbrandt,G;Friedman,MI
• 通讯作者: Friedman,MI