Hepatic phosphate trapping, decreased ATP, and increased feeding after 2,5-anhydro-D-mannitol

Autor: M. I. Friedman, H. Blum, Mary Osbakken, Nancy E. Rawson
Rok vydání: 1994
Předmět:
Zdroj: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 266:R112-R117
ISSN: 1522-1490
0363-6119
DOI: 10.1152/ajpregu.1994.266.1.r112
Popis: The mechanism by which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits feeding behavior was investigated by studying its metabolism and biochemical effects in liver. Thin-layer chromatography of liver extracts from rats given 2,5-AM containing 14C-labeled 2,5-AM showed that the analogue is phosphorylated in vivo with a time course that parallels the eating response. In vivo 31P nuclear magnetic resonance spectroscopy of rat liver during intravenous infusion of 2,5-AM and high-resolution nuclear magnetic resonance analyses of liver extracts showed that 2,5-AM is rapidly phosphorylated in liver, trapping hepatic phosphate and decreasing ATP, inorganic phosphate, and phosphate diesters. These changes occurred in a time frame in which the feeding response is elicited in conscious animals given the same dose of 2,5-AM by the same route. During an interval in which 2,5-AM increased eating, it also increased urinary uric acid excretion, implicating enhanced adenosine degradation in the reduction in hepatic ATP. These results provide the first direct evidence that changes in a high-energy phosphate-carrying compound in liver may provide a signal to initiate eating behavior.
Databáze: OpenAIRE