Fatty acid oxidation modulates the eating response to the fructose
analogue, 2,5-anhydro-d-mannitol.
Rawson, Nancy E., Patricia M. Ulrich, and Mark I. Friedman.
Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA
19104-3308
APStracts 3:0056R, 1996.
The fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), stimulates
feeding behavior in rats apparently through its effects on hepatic
energy metabolism, where it reduces glucose utilization, traps
phosphate and decreases ATP. The extent to which the magnitude and
duration of the eating response is dependent on the ability of the
liver to switch to fat oxidation for energy production was
investigated by manipulating substrate availability through dietary
and pharmacological means. Rats adapted to a high fat, low
carbohydrate diet preferentially utilize fat fuels for hepatic energy
production, and were insensitive to the effects of 2,5-AM on food
intake. The lack of an eating response occurred in spite of similar
changes in plasma fuels and liver glycogen, when compared to rats fed
a low fat, high carbohydrate diet. In contrast, inhibiting fatty acid
oxidation with methyl palmoxirate, which blocks transport of long
chain fatty acids into the mitochondria, potentiated the ability of
2,5-AM to stimulate feeding, without altering its effects on plasma
and liver fuels. These data demonstrate that the eating response to
2,5-AM is modulated by the availability of fat fuels, and implicates
a mechanism for initiation of feeding that is not dependent on
inhibition of carbohydrate metabolism per se, but rather integrates
information about the utilization of both types of fuels.
Received 3 November 1995; accepted in final form 9 February 1996.
APS Manuscript Number R685-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96