Ghrelin is produced primarily in the stomach in response to hunger, and 
circulates in the blood. Plasma ghrelin levels increase during fasting and 
decrease after ingesting glucose and lipid, but not protein. The efferent vagus 
nerve contributes to the fasting-induced increase in ghrelin secretion. Ghrelin 
secreted by the stomach stimulates the afferent vagus nerve and promotes food 
intake. Ghrelin also stimulates pituitary gland secretion of growth hormone (GH) 
via the afferent vagus nerve. GH inhibits stomach ghrelin secretion. These 
findings indicate that the vagal circuit between the central nervous system and 
stomach has a crucial role in regulating plasma ghrelin levels. Moreover, body 
mass index modulates plasma ghrelin levels. In a lean state and anorexia 
nervosa, plasma ghrelin levels are increased, whereas in obesity, except in 
Prader-Willi syndrome, plasma ghrelin levels are decreased and the feeding- and 
sleeping-induced decline in plasma ghrelin levels is disrupted. There are two 
forms of ghrelin: active n-octanoyl-modified ghrelin and des-acyl ghrelin. 
Fasting increases both ghrelin types compared with the fed state. Hyperphagia 
and obesity are likely to decrease plasma des-acyl ghrelin, but not 
n-octanoyl-modified ghrelin levels. Hypothalamic serum and 
glucocorticoid-inducible kinase-1 and serotonin 5-HT2C/1B receptor gene 
expression levels are likely to be proportional to plasma des-acyl ghrelin 
levels during fasting, whereas they are likely to be inversely proportional to 
plasma des-acyl ghrelin levels in an increased energy storage state such as 
obesity. Thus, a dysfunction of the ghrelin feedback systems might contribute to 
the pathophysiology of obesity and eating disorders.