To investigate the effects of yeast hydrolysate on appetite regulation mechanisms in the central nervous system, nitric oxide synthase (NOS) expression and vasoactive intestinal peptide (VIP) immunoreactivity in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH) of the hypothalamus were examined. Male Sprague-Dawley (SD) rats were assigned to five groups: control (normal diet), BY-1 and BY-2 (normal diet with oral administration of 0.1 g and 1.0 g of yeast hydrolysate <10 kDa/kg body weight, respectively), AY-1 and AY-2 (normal diet with oral administration of 0.1 g and 1.0 g of yeast hydrolysate 10-30 kDa/kg body weight, respectively). The body weight gain in the BY groups was less than that in the control. In particular, the weight gain of the BY-2 group (133.0 +/- 5.1 g) was significantly lower (p < 0.05) than that of the control group (150.1 +/- 3.7 g). Among the test groups, the BY-2 group was shown to have significantly lower triacylglycerol (TG) levels (p < 0.05) than the other groups. The staining intensities and optical densities of NOS neurons in the PVN of the AY group were significantly higher (p < 0.05) than in the control and BY groups. The staining intensities and optical densities of VIP immunoreactivity in the PVN and VMH of the BY groups were higher than those of the AY groups and the control. In conclusion, these results indicated that yeast hydrolysate of <10 kDa reduced the body weight gain and body fat in normal diet-fed rats and increased the lipid energy metabolism by altering the expression of NOS and VIP in neurons.