CHANGES IN ENERGY-METABOLISM AND METABOLITE PATTERNS OF OBESE RATS AFTER APPLICATION OF DEXFENFLURAMINE

Serotonergic neuronal networks are important for food intake and body weight regulation. Dexfenfluramine (dF), a serotonin releaser and reup take inhibitor, was used to investigate changes in food intake, body w eight development, energy expenditure, respiratory quotient, and subst rate oxidation rates for 12 days. Rats, which had been made obese by e arly postnatal overfeeding, received an energy-controlled mash diet an d water ad lib and were intraperitoneally injected daily with either s aline, 5 or 10 mg dF/kg. Compared to controls, food intake, body weigh t development, and energy expenditure were decreased in a dose-depende nt manner, especially during the first 6 days. Lipid oxidation was inc reased while oxidation of carbohydrates was decreased. Pair-feeding ex periments over 2 days revealed that this was not solely a result of di minished food intake but also an additional metabolic effect of dF, di fferent from its anorectic effect. At the end of these experiments, pl asma glucose and liver glycogen were unchanged after dF, but plasma fr ee fatty acids were significantly decreased. Insulin-sensitivity was p robably improved, indicated by decreased insulin levels and increases in muscle glycogen contents and activities of muscle pyruvate kinase. Liver-glutamine and contents of valine, leucine, and isoleucine in the muscle were significantly decreased after dF-treatment, the latter in dicating a diminished proteolysis. The plasma tryptophan/large neutral amino acids ratio of the dF-rats was unchanged but that of the paired -fed rats was changed, despite similar changes in food intake. It is c oncluded that both increased oxidation of endogenous fat and reduced f ood intake could mediate the body weight reducing effect of dF.