Serotonergic neuronal networks are important for food intake and
body weight regulation.
Dexfenfluramine (dF), a
serotonin releaser and reuptake inhibitor, was used to investigate changes in food intake,
body weight development, energy expenditure, respiratory quotient, and substrate oxidation rates for 12 days. Rats, which had been made obese by early postnatal overfeeding, received an energy-controlled mash diet and water ad lib and were intraperitoneally injected daily with either saline, 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 6 days.
Lipid oxidation was increased while oxidation of
carbohydrates was decreased. 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. At the end of these experiments, plasma
glucose and
liver glycogen were unchanged after dF, but plasma
free fatty acids were significantly decreased.
Insulin-sensitivity was probably 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 indicating 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 concluded that both increased oxidation of endogenous fat and reduced food intake could mediate the
body weight reducing effect of dF.