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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH050363-03
Application #
2249677
Study Section
Psychobiology and Behavior Review Committee (PYB)
Project Start
1993-08-01
Project End
1996-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Friedman, M I (1998) Fuel partitioning and food intake. Am J Clin Nutr 67:513S-518S
Ramirez, I; Tordoff, M G; Friedman, M I (1997) Satiety from fat? Adverse effects of intestinal infusion of sodium oleate. Am J Physiol 273:R1779-85
Rawson, N E; Ulrich, P M; Friedman, M I (1996) Fatty acid oxidation modulates the eating response to the fructose analogue 2,5-anhydro-D-mannitol. Am J Physiol 271:R144-8
Park, C R; Benthem, L; Seeley, R J et al. (1996) A comparison of the effects of food deprivation and 2,5-anhydro-D-mannitol on metabolism and ingestion. Am J Physiol 270:R1250-6
Friedman, M I; Ramirez, I; Tordoff, M G (1996) Gastric emptying of ingested fat emulsion in rats: implications for studies of fat-induced satiety. Am J Physiol 270:R688-92
Horn, C C; Tordoff, M G; Friedman, M I (1996) Does ingested fat produce satiety? Am J Physiol 270:R761-5
Boswell, T; Richardson, R D; Seeley, R J et al. (1995) Regulation of food intake by metabolic fuels in white-crowned sparrows. Am J Physiol 269:R1462-8
Park, C R; Seeley, R J; Benthem, L et al. (1995) Whole body energy expenditure and fuel oxidation after 2,5-anhydro-D-mannitol administration. Am J Physiol 268:R299-302
Friedman, M I (1995) Control of energy intake by energy metabolism. Am J Clin Nutr 62:1096S-1100S
Rawson, N E; Ulrich, P M; Friedman, M I (1994) L-ethionine, an amino acid analogue, stimulates eating in rats. Am J Physiol 267:R612-5