Abstract
Since plasma ghrelin can undergo des-acylation and proteolysis, the aim of this work was to investigate the extent to which enhancement of these reactions is associated with the decrease of ghrelin in plasma after food intake or in individuals with obesity. Unique analogs of natural ghrelin were developed to monitor changes in plasma ghrelin levels. Levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation, and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 people (n=21 males) with normal weight (NW, n=20) or overweight/obesity (OW/OB, n=20). Preprandial ghrelin and DAG levels were lower, whereas preprandial ghrelin proteolysis was approximately 4.6-fold higher in the plasma of males that were OW/OB. Ghrelin proteolysis in males positively correlated with glycemia. Ghrelin and DAG levels were also lower in females with NW or OW/OB. Ghrelin and DAG levels decreased postprandially in males and females, independently of BMI, and ghrelin proteolysis increased postprandially approximately 2 folds only in individuals with NW. Ghrelin des-acylation remained unaffected by BMI or feeding status in both sexes. This current study highlights that ghrelin proteolysis increases in males with obesity as well as after a meal in lean individuals. Therefore ghrelin proteolysis may be an important checkpoint and, consequently, a putative pharmacological target to control circulating ghrelin levels in humans.