It has been proposed that the turnover of metabolic fuels affects feeding. In the present study the effects of different metabolites (glycerol, L-malate, D-3-hydroxybutyrate, L-lactate) or their oxidation products (dihydroxyacetone, oxaloacetate, acetoacetate, pyruvate) on food intake were investigated under various feeding conditions. The results of these experiments increase our knowledge about the nature and origin of metabolic signals in the energostatic control of food intake. In the experiments, glycerol, malate, 3-hydroxybutyrate, lactate or pyruvate (4.5-7.7 mmoles/kg metabolic body weight injected subcutaneously reduced food intake in rats, whereas dihydroxyacetone, acetoacetate or oxaloacetate did not. The effect of glycerol disappeared with high levels of dietary protein, whereas the effects of lactate and pyruvate disappeared with high levels of dietary fat. The hypophagic effects of glycerol, malate, 3-hydroxybutyrate, lactate and pyruvate were abolished by selective hepatic vagotomy. The results suggest that vagally mediated signals originating from hepatic oxidation of metabolic fuels contribute to the regulation of food intake.