2,5-anhydro-D-mannitol acts in liver to initiate feeding.

We determined the site at which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) acts to increase food intake in rats. Rats began eating sooner and ate more food during hepatic portal than during jugular infusions of 2,5-AM (50, 100, or 150 mg/h). After rats were intubated with 2,5-[14C]AM (1.15 microCi in 200 mg/kg), significant quantities of radioactivity were found in liver but not in brain. Hepatic vagotomy prevented the eating response to 200 mg/kg 2,5-AM without altering the effect of the analogue on plasma fuels. These results indicate that low doses of 2,5-AM act in the liver to increase food intake and suggest that the signal for feeding generated in the liver is transmitted to the brain through the hepatic vagus nerve. Taken together, this work provides the strongest evidence to date that a signal initiating feeding behavior originates in the liver.