High-fat diet prevents eating response and attenuates liver ATP decline in rats given 2,5-anhydro-D-mannitol.
Administration of the fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates eating in rats fed a low-fat diet but not in those fed a high-fat diet that enhances fatty acid oxidation. The eating response to 2,5-AM treatment is apparently triggered by a decrease in liver ATP content. To assess whether feeding a high-fat diet prevents the eating response to 2,5-AM by attenuating the decrease in liver ATP, we examined the effects of the analog on food intake, liver ATP content, and hepatic phosphate metabolism [using in vivo 31P-NMR spectroscopy (NMRS)]. Injection (intraperitoneal) of 300 mg/kg 2,5-AM increased food intake in rats fed a high-carbohydrate/low-fat diet, but not in those fed high-fat/low-carbohydrate (HF/LC) food. Liver ATP content decreased in all rats given 2,5-AM compared with saline, but it decreased about half as much in rats fed the HF/LC diet. NMRS on livers of anesthetized rats indicated that feeding the HF/LC diet attenuates the effects of 2,5-AM on liver ATP by reducing phosphate trapping. These results suggest that rats consuming a high-fat diet do not increase food intake after injection of 2,5-AM, because the analog is not sufficiently phosphorylated and therefore fails to decrease liver energy status below a level that generates a signal to eat.
Friedman
Mark I
MI
Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA. friedman@monell.org
Koch
James E
JE
Graczyk-Milbrandt
Grazyna
G
Ulrich
Patricia M
PM
Osbakken
Mary D
MD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley
D004041:Dietary Fats; D010758:Phosphorus; D008353:Mannitol; C031765:2,5-anhydromannitol; D000255:Adenosine Triphosphate