METABOLIC CONTROL OF FEEDING BEHAVIOR

拟议的研究涉及的基本问题的性质， 控制食物摄入的代谢信号。 初步研究表明 肝脏中的生化事件与葡萄糖代谢和 脂肪酸提供了进餐开始的综合信号。 ATP， 它可以潜在地提供这样的信号，已经被建议作为一种 刺激的控制喂养，但这一假设一直没有得到 直接测试。 利用果糖的初步实验 类似物，2，5-脱水-D-甘露醇（2，5-AM），涉及肝细胞减少 ATP水平作为进餐开始的信号。 拟议的实验 将研究三磷酸腺苷（ATP）及其代谢产物的作用 控制老鼠的进食行为。 行为测量， 沿着31 p核磁共振谱和高压 液相色谱法，将用于（1）评估降低的作用 给药诱发进食时肝脏ATP水平的变化 （2）评估肝细胞癌与代谢抑制剂的关系。 磷酸盐和ATP水平以及对2，5-AM的进食反应;（3）确定 肝脏钠-磷酸盐共转运在进食反应中的作用 （4）确定肝脏ATP水平与2，5-AM的关系， 慢性实验性糖尿病的食欲过盛;和（5）确定 肝脏ATP水平与食物摄入量之间的关系 斋戒. 这些研究将有助于阐明 食物摄入量，因此将有助于更全面地了解 厌食、暴饮暴食和肥胖的病因，以及发展 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.