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Am J Physiol Regul Integr Comp Physiol 282: R710-R714, 2002; doi:10.1152/ajpregu.00156.2001
0363-6119/02 $5.00
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Vol. 282, Issue 3, R710-R714, March 2002

High-fat diet prevents eating response and attenuates liver ATP decline in rats given 2,5-anhydro-D-mannitol

Mark I. Friedman1, James E. Koch1, Grazyna Graczyk-Milbrandt1, Patricia M. Ulrich1, and Mary D. Osbakken2

1 Monell Chemical Senses Center and 2 University of Pennsylvania, Department of Biochemistry & Biophysics, Philadelphia, Pennsylvania 19104

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.

feeding behavior; fuel metabolism; nuclear magnetic resonance


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