Hepatic phosphate trapping, decreased ATP, and increased feeding after 2,5-anhydro-D-mannitol.
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.
Rawson
N E
NE
University of Pennsylvania, Philadelphia.
Blum
H
H
Osbakken
M D
MD
Friedman
M I
MI
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002855:Chromatography, Thin Layer; D004435:Eating / Q000187:drug effects*; D004952:Esters / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000652:urine
D004952:Esters; D010710:Phosphates; D014527:Uric Acid; D010758:Phosphorus; D008353:Mannitol; C031765:2,5-anhydromannitol; D000255:Adenosine Triphosphate