DISPARATE EFFECTS OF FENFLURAMINE ON THERMOGENESIS IN BROWN ADIPOSE-TISSUE IN THE RAT

It has been suggested that fenfluramine, a clinically used appetite su ppressant, can also promote weight loss by augmenting energy expenditu re, as indicated by increased whole-body O2 consumption (Vo2) and mito chondrial GDP binding in brown adipose tissue (BAT) of fenfluramine-tr eated rats. To further investigate a possible involvement of BAT in th e drug's metabolic effects, Sn-113-labelled microspheres were injected into the left cardiac ventricle of conscious rats 70-80 min after int raperitoneal delivery of 20 mg/kg fenfluramine (DL-mixture) or saline vehicle. At 28-degrees-C ambient temperature, fenfluramine augmented r esting whole-body Vo2 and increased the microsphere entrapment in BAT, indicating enhanced blood flow and metabolism. At 20-degrees-C ambien t temperature, the expected increase in BAT blood flow associated with nonshivering thermogenesis was observed in control rats, but in fenfl uramine-treated rats the increase in BAT blood flow was severely atten uated, and Vo2 and body temperature were reduced. The stimulatory effe ct of fenfluramine on BAT metabolism was not prevented by urethane ane sthesia but did not occur if the tissue was denervated. These blood fl ow measurements corroborate previous reports, based on GDP-binding ass ays, that fenfluramine treatment can augment thermogenesis in BAT by e ffects mediated through the innervation of the tissue. However, the da ta also indicate that this calorigenic effect is dependent on ambient temperature being near thermoneutrality and that in a cool environment the drug inhibits BAT thermogenesis.