METABOLIC CONTROL OF FEEDING BEHAVIOR

拟议的研究解决了基本的问题，即 控制食物摄入量的代谢信号。初步研究表明 肝脏中葡萄糖代谢的共同生化事件和 脂肪酸为进餐的开始提供了一个完整的信号。三磷酸腺苷， 它可能会提供这样的信号，被认为是一种 用于控制喂食的刺激，但这一假说尚未得到 直接测试。利用果糖的初步试验 类似物，2，5-脱水-D-甘露醇(2，5-AM)，意味着肝脏的减少 ATP水平作为进餐开始的信号。拟议中的实验 将研究三磷酸腺苷(ATP)及其代谢物的作用 在控制大鼠的摄食行为方面。行为测量， 以及31P核磁共振波谱和高压 采用高效液相色谱法，将其用于(1)评价降糖作用 服药诱导进食过程中肝脏ATP水平的变化 代谢抑制剂；(2)评估肝脏与 磷酸盐和ATP水平与对2，5-AM的进食反应；(3)确定 肝脏钠磷共转运在进食反应中的作用 至2，5-AM；(4)测定肝组织ATP水平与 慢性实验性糖尿病的吞噬功能亢进；以及(5)测定 肝组织三磷酸腺苷水平与食物摄入量的关系 禁食。这些研究将有助于阐明维生素C的代谢控制。 食物的摄入量，因此将有助于更全面地了解 厌食症、暴饮暴食、肥胖的病因及其与发病的关系 制定适当的预防和治疗战略。

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.