Decreased inhibition by leptin of hypothalamic arcuate neurons in neonatally overfed young rats

Rats neonatally overnourished due to a reduced litter size develop persisting overweight throughout life. A presumed mechanism leading to this 'malprogramming' consists of an acquired change of the responsiveness to leptin of the neuronal system regulating feeding behavior. The study reports significant differences in the effects of leptin on single unit activity of the arcuate nucleus in brain slices of normal compared with early postnatally overfed juvenile rats. The firing rate of arcuate neurons in normal rats was inhibited by leptin (Wilcoxon test p < 0.0001 n = 42), whereas it was not changed in obese rats (Wt p = 2.4, n = 35). The reduced inhibition by leptin of arcuate neurons in neonatally overfed rats might indicate an acquired hypothalamic leptin resistance contributing to persistent hyperphagia and overweight. NeuroReport 11:2795-2798 (C) 2000 Lippincott Williams & Wilkins.