METABOLIC CONTROL OF FEEDING BEHAVIOR

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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.