Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism

Ghrelin, a hormone whose levels increase during food deprivation, plays a pivotal role in the regulation of food intake, energy metabolism and storage, as well as in insulin sensitivity. Here, we investigated the effects of acyl-ghrelin neutralization with the acyl-ghrelin-binding compound NOX-B11(2) during the fasting-refeeding cycle. Our data demonstrate that ghrelin neutralization with NOX-B11(2) impairs recuperation of lost body weight after food deprivation. Analysis of enzymes involved in glucose and lipid metabolism in liver of fed, fasted and refed rats revealed that neutralization of acyl-ghrelin resulted in minor decreases in the enzymes of glycolytic and lipogenic pathways during fasting. However, during refeeding these enzymes as well as glycogen levels recovered more slowly when acyl-ghrelin was blocked. The high levels of ghrelin in response to food deprivation may contribute to an adequate decrease in hepatic glycolytic and lipogenic enzymes and aid in the recovery of body weight and energetic reserves once food becomes available after the fasting period.