ENERGY-METABOLISM AND METABOLITE PATTERNS OF RATS AFTER APPLICATION OF DEXFENFLURAMINE

Serotoninergic neuronal networks are important for food intake and bod y weight regulation. However, the mechanisms by which some metabolic p athways are influenced are rather unclear. Dexfenfluramine (DF), a ser otonin releaser and re-uptake inhibitor, was used to investigate chang es in food intake, body weight development, energy expenditure, respir atory quotient and substrate oxidation rates for 12 days. Normal rats, receiving an energy-controlled mash diet and water ad libitum were in traperitoneally injected daily with either saline, 1, 2.5, 5 or 10mg n F/kg. Compared to controls, food intake, body weight development and e nergy expenditure were decreased in a dose-dependent manner, especiall y during the first six days. Lipid oxidation was increased while oxida tion of carbohydrates was decreased. Pair-feeding experiments over thr ee days revealed that this was a clear pharmacological effect and not simply a result of diminished food intake. At the end of these experim ents, plasma glucose and liver and muscle glycogen were unchanged afte r DF, but isoleucine, leucine and lysine were significantly decreased in plasma and liver. Therefore, the plasma tryptophan/ large neutral a mino acids ratio was slightly increased. Protein oxidation was unchang ed after of. It is concluded that a prompt decline in energy expenditu re with increased fat oxidation rates could mediate the body weight re ducing effect of DF.