Ghrelin, an acylated upper gastrointestinal
peptide, is the only known orexigenic
hormone. Considerable evidence implicates
ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial
ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues.
Ghrelin injections stimulate food intake rapidly and transiently, primarily by increasing appetitive feeding behaviors and the number of meals. Preprandial
ghrelin surges are probably triggered by sympathetic nervous output. Postprandial suppression is not mediated by nutrients in the stomach or duodenum, where most
ghrelin is produced. Rather, it results from post-ingestive increases in lower intestinal osmolarity (information probably relayed to the foregut via enteric nervous signaling), as well as from
insulin surges. Consequently, ingested
lipids suppress
ghrelin poorly compared with other macronutrients. Beyond a probable role in meal initiation,
ghrelin also fulfills established criteria for an adiposity-related
hormone involved in long-term
body-weight regulation.
Ghrelin levels circulate in relation to energy stores and manifest compensatory changes in response to
body-weight alterations.
Ghrelin crosses the blood-brain barrier and stimulates food intake by acting on several classical
body-weight regulatory centers, including the hypothalamus, hindbrain, and mesolimbic reward system. Chronic
ghrelin administration increases
body weight via diverse, concerted actions on food intake, energy expenditure, and fuel utilization. Congenital ablation of the
ghrelin or
ghrelin-receptor gene causes resistance to diet-induced
obesity, and pharmacologic
ghrelin blockade reduces food intake and
body weight.
Ghrelin levels are high in
Prader-Willi syndrome and low after
gastric bypass surgery, possibly contributing to
body-weight alterations in these settings. Extant evidence favors roles for
ghrelin in both short-term meal initiation and long-term energy homeostasis, making it an attractive target for drugs to treat
obesity and/or wasting disorders.