Increased inhibition by agouti-related peptide of ventromedial hypothalamic neurons in rats overweight due to early postnatal overfeeding.

Melanocortins, e.g. alpha-melanocyte stimulating hormone, are involved in the central nervous regulation of body weight. Agouti-related peptide (AGRP) as an endogenous melanocortin receptor antagonist induces feeding. Overexpression leads to obesity. Rats that grow up in small litters develop persistent hyperphagia and are overweight throughout life. Changes in the neuronal activity of the ventromedial hypothalamic nucleus (VMH) that signals satiety with activation might be involved. We studied single unit activity in hypothalamic brain slices. Melanocortins activated or inhibited similarly in control and small litter rats. AGRP mainly inhibited VMH neurons of overweight rats (t-test, P < 0.005, n = 33), whereas it also activated neurons of controls. This increased inhibition of VMH neurons by AGRP in early postnatally overnourished rats might contribute to the changed regulation leading to a persistent overweight condition throughout life.