ENERGY-EXPENDITURE AND SUBSTRATE OXIDATION RATES OF OBESE RATS DURINGA 12-DAY TREATMENT WITH DEXFENFLURAMINE

Serotoninergic neuronal networks are included in regulation and modifi cation of eating behavior and energy metabolism. Dexfenfluramine (dF), a serotonin releaser and reuptake inhibitor, was used to investigate changes in food intake, body weight development, energy expenditure, r espiratory quotient, and substrate oxidation rates for 12 days. Rats w hich had been made obese by postnatal overfeeding received an energy-c ontrolled mash diet and water ad libitum and were intraperitoneally in jected with either saline or 5 or 10 mg dF/kg. As compared with contro ls, food intake and energy expenditure were significantly decreased in a dose-dependent manner, especially during the first 6 days. Lipid ox idation was increased, while the oxidation of carbohydrates was decrea sed. The body weight was only slightly reduced after 2 days of dF trea tment. After 4 days, dF-treated rats resumed body weight, but as compa red with controls both dF groups exhibited lower body weights at the e nd of the experiment. After 12 days the plasma glucose concentration w as unchanged, whereas plasma free fatty acids were significantly decre ased. Plasma insulin levels were unchanged after dF, but 10 mg dF/kg l ed to increased muscle and, especially, liver glycogen contents, indic ating an improved nonoxidative glucose disposal. Muscle pyruvate kinas e was slightly but not significantly increased after dF treatment but that of the liver was significantly decreased, indicating a reduced gl ycolytic activity of the liver. Whereas the renal N excretion was rath er decreased, the plasma concentrations of urea, citrulline, arginine, and ornithine were increased, and the liver contents of glutamine and arginine were decreased. Possibly, there is a shift of ammonia remova l from glutamine synthesis to production of urea. The sum of all large neutral amino acids in muscle was significantly decreased after dF tr eatment, indicating a diminished proteolysis. Pair-feeding experiments over 2 days revealed that this was not solely a result of diminished food intake, but also an additional metabolic effect of dF, different from its anorectic effect. It is concluded that both increased oxidati on of endogenous fat and reduced food intake could mediate the body we ight reducing effect of dF.