Energy metabolism and metabolite patterns of rats after application of dexfenfluramine

Serotoninergic neuronal networks are important for food intake and body weight regulation. However, the mechanisms by which some metabolic pathways are influenced are rather unclear. Dexfenfluramine (DF), a serotonin releaser and re-uptake inhibitor, was used to investigate changes in food intake, body weight development, energy expenditure, respiratory quotient and substrate oxidation rates for 12 days. Normal rats, receiving an energy-controlled mash diet and water ad libitum were intraperitoneally injected daily with either saline, 1, 2.5, 5 or 10 mg DF/kg. Compared to controls, food intake, body weight development and energy expenditure were decreased in a dose-dependent manner, especially during the first six days. Lipid oxidation was increased while oxidation of carbohydrates was decreased. Pair-feeding experiments over three days revealed that this was a clear pharmacological effect and not simply a result of diminished food intake. At the end of these experiments, plasma glucose and liver and muscle glycogen were unchanged after DF, but isoleucine, leucine and lysine were significantly decreased in plasma and liver. Therefore, the plasma tryptophan/large neutral amino acids ratio was slightly increased. Protein oxidation was unchanged after DF. It is concluded that a prompt decline in energy expenditure with increased fat oxidation rates could mediate the body weight reducing effect of DF.