Conditional deletion of brain-derived neurotrophic factor in the postnatalbrain leads to obesity and hyperactivity

Brain-derived neurotrophic factor has been associated previously with the r egulation of food intake. To help elucidate the role of this neurotrophin i n weight regulation, we have generated conditional mutants in which brain-d erived neurotrophic factor has been eliminated from the brain after birth t hrough the use of the cre-loxP recombination system. Brain-derived neurotro phic factor conditional mutants were hyperactive after exposure to stressor s and had higher levels of anxiety when evaluated in the light/dark explora tion test. They also had mature onset obesity characterized by a dramatic 8 0-150% increase in body weight, increased linear growth, and elevated serum levels of leptin, insulin, glucose, and cholesterol. In addition, the muta nts had an abnormal starvation response and elevated basal levels of POMC, an anorexigenic factor and the precursor for a-MSH. Our results demonstrate that brain derived neurotrophic factor has an essential maintenance functi on in the regulation of anxiety-related behavior and in food intake through central mediators in both the basal and fasted state.