Deranged Secretion of Ghrelin and Obestatin in the Cephalic Phase of Vagal Stimulation in Women with Anorexia Nervosa

Abstract

Vagal activation in the cephalic phase response to food ingestion promotes ghrelin secretion. Because underweight individuals with anorexia nervosa (AN) are characterized by increased vagal tone, we hypothesized an enhanced ghrelin production in the cephalic phase of vagal stimulation. Therefore, we investigated the responses of ghrelin and its recently discovered sibling peptide obestatin to modified sham feeding (MSF) in both AN and healthy women. Eight AN women and eight age-matched healthy female subjects underwent MSF, with initially seeing and smelling a meal and then chewing the food without swallowing it. Blood samples were drawn before and after MSF for hormone assays. Circulating ghrelin increased, whereas obestatin decreased after MSF. Compared with healthy women, AN individuals exhibited enhanced ghrelin and obestatin baseline plasma levels and amplified MSF-induced ghrelin increase and obestatin drop. Ghrelin secretion positively correlated with subjects' eating behavior as assessed by the Three-Factor Eating Questionnaire. Opposite changes in circulating ghrelin and obestatin occur in the cephalic phase of vagal stimulation, and these changes are amplified in symptomatic AN patients. Given the opposite effects of ghrelin and obestatin on food intake, these findings may have pathophysiologic implications for the dysregulated eating behavior of AN individuals.