L-ethionine, an amino acid analogue, stimulates eating in rats

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) triggers feeding in rats through its actions in liver, which include a decrease in ATP due to trapping of phosphate. To determine whether decreasing liver ATP by a different means would also trigger feeding, we gave rats L-ethionine (ETH), an amino acid analogue that reduces ATP in liver by trapping adenosine as S-adenosyl-L-ethionine. ETH-treatment increased food intake from 4 to 8 h after administration, without affecting 24-h intake. Two hours after treatment, liver ATP was 25% lower in rats given ETH than in vehicle-treated controls. Circulating fuels and liver lactate and pyruvate were not affected by ETH treatment, whereas liver glycogen was 15% lower in ETH-treated rats. These results are the first to show that an amino acid analogue elicits feeding in rats fed protein-sufficient diets. Because a decrease in liver ATP is the only common effect of ETH and 2,5-AM observed thus far, a signal related to liver ATP status may be involved in the mechanism for initiation of feeding in rats.