Differences in the increase in food intake and the activation of neurons of the appetite-control network in the central nervous system between 24-hour fasted and fed rats by peripheral ghrelin administration

Background: Ghrelin is the only hormone that increases appetite. Ghrelin is also known to promote physiologically the start of food intake. Using 24-hour fasted or fed rats, the differences in the effects of ghrelin on appetite and the activation of the brain appetite regulation network between these two groups were examined.<br> Method: These two groups of rats were administered with ghrelin intraperitoneally, and the difference in dose-dependent effects on the amount of food was examined. Furthermore, immunostaining with an anti-c-Fos antibody was carried out to evaluate the expression of the c-Fos protein, which is an index of neuronal activation, on the neurons of the nuclei in the hypothalamus and reward systems constituting the appetite regulation network in the brain. In addition, concentrations of glucose, insulin and leptin in the collecting blood of both groups of rats were also assayed immediately after fasting for 24 hours or feeding.<br> Results: The dose-dependent effects of intraperitoneal administration of ghrelin at 10, 30, 50, and 100 μg/kg rat body weight on food intake were examined. The maximum effect was observed at 50 μg/kg in both groups. When the effect on increasing food intake between the two groups was compared, a larger increase in food intake was observed in rats that fasted for 24 hours than in the fed group. In the experiment with immunostaining of c-Fos in the neurons of the brain, ghrelin 50 μg/kg administered intraperitoneally increased the number of c-Fos-positive cells in the both groups in the arcuate nucleus (ARC) and nucleus accumbens (NAc), but significant increase in the number of c-Fos-positive cells in the lateral hypothalamus (LH) and ventral tegmental area (VTA) was observed in the 24-hour fasted group. Furthermore, the concentrations of glucose, insulin, and leptin in the blood were measured in both groups, but significantly high levels in all three were observed in the fed group.<br> Conclusions: The results suggest that the orexigenic effect of ghrelin by peripheral administration is more enhanced in the fasted group compared to that in the fed group and that the mechanism for the difference in the effect of ghrelin is supposed to be due to the responsiveness of these neuronal nuclei such as LH of the hypothalamus and VTA of the reward system in the appetite-control network.