CHARACTERISTICS OF BDNF-INDUCED WEIGHT-LOSS

There is evidence that central infusion of brain-derived neurotrophic factor (BDNF) induces weight loss in rats. We have begun to investigat e the physiological basis for BDNF-induced weight loss by assessing it s relationship to (a) appetite, (b) serum indices of metabolic and ren al toxicity, and (c) brain monoamine activity in areas associated with feeding or motor function. BDNF (0-6 mu g/day) was infused into the l ateral ventricle (LV) of male Long-Evans rats for 14 days. Body weight and food intake were monitored throughout infusion and recovery perio ds. BDNF induced severe, dose dependent appetite suppression and weigh t loss. Although appetite began to recover after the 10th infusion day , body weight had not returned to control values at the end of the rec overy period. The weight loss observed in BDNF-infused rats was relate d to appetite suppression, since uninfused rats that were pair-fed to high dose BDNF-treated rats showed comparable weight loss. Despite sev ere weight loss, serum BUN, creatinine, thyroxine, glucose, and total protein were not affected by BDNF infusion. Striatal DO-PAC/DA was sim ilarly unaffected by BDNF. In contrast, BDNF-infused rats showed a dos e-dependent increase in hypothalamic 5-HIAA/5-HT that was not observed in pair-fed rats, suggesting that the observed increase in hypothalam ic 5-HIAA/5-HT was a direct effect of BDNF infusion rather than a seco ndary effect of food restriction. These data suggest that BDNF may ind uce appetite suppression and weight loss through a central mechanism. (C) 1995 Academic Press, Inc.