Acyl-modification of ghrelin regulates its appetite-stimulating activity in mice

Abstract

Ghrelin is an acylated brain-gut hormone secreted primarily from stomach. The major active form of ghrelin is a 28-amino acid peptide with an n-octanoyl (C8) modification at Ser3 residue. There also exist other acylated forms of ghrelin, such as n-decanoyl (C10) ghrelin. The previous study demonstrated that intravenous administration of C8-ghrelin increases appetite and food consumption in rodents. To elucidate effects of acyl-modified ghrelins on appetite, we have therefore measured concentrations of acylated ghrelins in stomach and plasma of control and fasted mice. In control, the C8-ghrelin concentration in stomach was higher than the C10-ghrelin. In 48h-fasted mice, the C8-ghrelin significantly decreased whereas the C10-ghrelin significantly increased. Consequently, the C10-ghrelin was greater than the C8-ghrelin in plasma of 48h-fasted mice. Intraperitoneal (ip) injection and intracerebroventricular (icv) injection of C8- or C10-ghrelin significantly facilitated the food consumption 2h after the injection. Ip injection of either C8- or C10-ghrelin had a similar effect. On the other hand, 2h after icv injection of C8-ghrelin, the food consumption was greater than that 2h after icv injection of C10-ghrelin. These results suggest that the condition of energy metabolism influences the acyl-modification of ghrelin, and C10-ghrelin has a site-dependent activity for the stimulation of appetite in mice. [J Physiol Sci. 2006;56 Suppl:S100]