Etomoxir, a fatty acid oxidation inhibitor, increases food intake and reduces hepatic energy status in rats

Etomoxir, an inhibitor of fatty acid oxidation, increases food intake and reported hunger in humans. Work with animal models suggests that other inhibitors of fatty acid oxidation stimulate feeding behavior by acting on the liver. In the following study, we assessed whether etomoxir would increase food intake in rats and to what degree the effects of etomoxir on feeding were associated with changes in hepatic energy status. The effects of etomoxir on hepatic energy status were assessed by measuring liver ATP, ADP, phosphorylation potential, and glycogen content. Blood glucose, free fatty acids, and ketone bodies were also measured to determine the availability of circulating fuels following etomoxir treatment. Etomoxir and methyl palmoxirate (MP; another inhibitor of fatty acid oxidation) increased food intake. Etomoxir, like MP, also reduced hepatic ATP/ADP ratio and phosphorylation potential. In combination with 2,5-anhydro-D-mannitol (an analogue of fructose that produces an increase in feeding by action on the liver), etomoxir synergistically increased food intake and reduced hepatic ATP/ADP ratio. In summary, etomoxir increased food intake and decreased hepatic energy status in the rat. This suggests that etomoxir stimulates feeding by action on the liver.