Effect of fenfluramine on GDP-binding to brown adipose tissue mitochondria

These experiments have tested the effects of treatment with fenfluramine on the GDP-binding to mitochondria isolated from interscapular brown adipose tissue in vitro. In acute studies, the binding of GDP was significantly increased after 3, 24, and 48 hours of treatment with a single dose of 20 mg/kg of body weight. Addition of fenfluramine in vitro, however was without effect. In a dose-response study there was no significant increase with doses of 2 or 6 mg/kg but there was a significant increase at 20 mg/kg. During eleven days of treatment, food intake was initially depressed by fenfluramine (20 mg/kg) and body weight was significantly reduced. By the ninth day of treatment however, food intake had returned to control values but the body weight remained significantly lower than in the control group. The weight of interscapular brown adipose tissue was not significantly altered but binding of GDP to isolated mitochondria was increased by 55%. These studies suggest a thermogenic effect of fenfluramine on the brown adipose tissue of rats.