Fatty acid oxidation affects food intake by altering hepatic energy status

Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl p almoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration o f 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. in contrast, feeding behavior increased in rats giv en 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the sa me extent as did the low dose but in addition suppressed fatty acid oxidati on in muscle and produced a marked depletion of liver glycogen. Dose-relate d increases in food intake tracked dose-related reductions in liver ATP con tent, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding beha vior by reducing hepatic energy production.