Metabolic inhibitors synergistically decrease hepatic energy status and increase food intake

Previous studies indicate that administration of the metabolic inhibitor, 2,5-anhydro-D-mannitol (2,5-AM) or methyl palmoxirate (MP), induces feeding behavior in rats by lowering hepatic energy status. Combined treatment with these agents synergistically increases food intake. The present study was designed to investigate whether combined treatment also has a synergistic effect on hepatic energy status. Rats treated with both inhibitors increased feeding behavior compared with the controls, whereas those treated with 2, 5-AM or MP alone did not. Although 2,5-AM alone lowered hepatic ATP content regardless of MP treatment, only the combination resulted in decreases in hepatic ATP/ADP ratio and phosphorylation potential. MP treatment did not affect the uptake of 2,5-AM into liver. These results suggest that a reduction in hepatic energy status is the common triggering signal for eating behavior induced by 2,5-AM and MP and provide additional evidence for an integrated metabolic control of food intake.