METABOLIC CONTROL OF FEEDING BEHAVIOR

进食行为的代谢控制

• 批准号: 2249676
• 负责人: MARK FRIEDMAN
• 金额: $ 22.43万
• 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 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2249676
• 关键词: adenosine triphosphate; antiport; biological signal transduction; diabetes mellitus; fasting; fatty acid metabolism; glucose metabolism; high performance liquid chromatography; laboratory rat; liver metabolism; mannitol; nuclear magnetic resonance spectroscopy; nutrient intake activity; nutrition related tag; ouabain; overeating; phosphates; psychobiology

The proposed studies address the basic question of the nature of the metabolic signals that control food intake. Preliminary studies suggest that a biochemical event in liver common to the metabolism of glucose and fatty acids provides an integrated signal for meal initiation. ATP, which could potentially provide such a signal, has been suggested as a stimulus for the control of feeding, but this hypothesis has not been tested directly. Preliminary experiments utilizing the fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), implicate a decrease in liver ATP levels as a signal for meal initiation. The proposed experiments will examine the role of adenosine triphosphate (ATP) and its metabolites in the control of feeding behavior in rats. Behavioral measurements, along with 31p nuclear magnetic resonance spectroscopy and high pressure liquid chromatography, will be used to (1) Assess the role of decreased hepatic ATP level in the elicitation of eating induced by administration of metabolic inhibitors; (2) Assess the relationship between hepatic phosphate and ATP levels and the eating response to 2,5-AM; (3) Determine the role of hepatic sodium-phosphate co-transport in the eating response to 2,5-AM; (4) Determine the relationship between hepatic ATP levels and the hyperphagia in chronic experimental diabetes; and (5) Determine the relationship between hepatic ATP levels and food intake in response to fasting. These studies will help to elucidate the metabolic control of food intake and therefore will contribute to a fuller understanding of the etiology of anorexia, overeating and obesity, and to the development of appropriate strategies for their prevention and treatment.

拟议的研究解决了本质的基本问题 控制食物摄入的代谢信号。 初步研究表明 肝脏中常见的肝脏代谢和 脂肪酸为膳食开始提供了一个集成的信号。 ATP， 可能会提供这样的信号，已被建议 控制喂养的刺激，但该假设尚未 直接测试。 利用果糖的初步实验 类似物，2,5-Anhydro-d-annitol（2,5-AM），暗示肝脏降低 ATP水平是膳食启动的信号。 提出的实验 将检查三磷酸腺苷（ATP）及其代谢产物的作用 控制大鼠的喂养行为。 行为测量， 以及31p的核磁共振光谱和高压 液相色谱法将用于（1）评估降低的作用 肝ATP水平在诱导的饮食中诱导 代谢抑制剂； （2）评估肝之间的关系 磷酸盐和ATP水平以及对2,5-AM的饮食反应； （3）确定 肝磷酸钠共转运在饮食反应中的作用 到2,5-AM; （4）确定肝ATP水平和 慢性实验性糖尿病中的脾气； （5）确定 肝ATP水平与食物摄入量之间的关系 禁食。 这些研究将有助于阐明 食物摄入量，因此将有助于更深入地了解 厌食，暴饮暴食和肥胖的病因以及发展 适当的预防和治疗策略。