Different metabolites might reduce food intake by the mitochondrial generation of reducing equivalents.

To test the possibility that hypophagic effects of injected metabolites are linked to a particular oxidative step in their metabolism, cumulative food intake in rats after subcutaneous injection of various metabolites or their immediate oxidation products was investigated. Glycerol was compared with dihydroxyacetone, L-malate with oxaloacetate, and L-lactate with pyruvate. Subcutaneous injection of 4.5 mmol/kg metabolic body weight (BW0.75) of glycerol or malate reduced food intake significantly, whereas the same doses of dihydroxyacetone or oxaloacetate did not. Lactate or pyruvate (4.5 mmol/kg BW0.75, each) both reduced food intake significantly. However, even higher doses (7.7 mmol/kg BW0.75) of lactate or pyruvate failed to affect food intake when rats were fed a high fat (HF) diet, which is known to decrease the activity of the enzyme pyruvate dehydrogenase. In an additional experiment, subcutaneous injection of lactate or pyruvate (7.7 mmol/kg BW0.75, each) increased plasma levels of lactate and pyruvate 2 h after the injection in HF-rats more than in rats fed the usual high-carbohydrate diet. The data are consistent with the hypothesis that the increased generation of reducing equivalents in the mitochondria, brought about by the oxidation of injected glycerol, malate, lactate, or pyruvate, reduces food intake in rats.