Ghrelin as a Survival Hormone

Ghrelin administration induces food intake and body weight gain. Based on these actions, the ghrelin system was initially proposed as an antiobesity target. Subsequent studies using genetic mouse models have raised doubts about the role of the endogenous ghrelin system in mediating body weight homeostasis or obesity. However, this is not to say that the endogenous ghrelin system is not important metabolically or otherwise. Here we review an emerging concept in which the endogenous ghrelin system serves an essential function during extreme nutritional and psychological challenges to defend blood glucose, protect body weight, avoid exaggerated depression, and ultimately allow survival. The ghrelin system comprises three main components: ghrelin, the ghrelin receptor (the growth hormone secretagogue receptor), and ghrelin-O-acyltransferase (GOAT). Endogenous ghrelin is involved in food anticipatory and food reward behavior but may not play a conspicuous orexigenic role when food availability is plentiful or in diet-induced obese states. The ghrelin system is essential during certain nutritional and psychological challenges including caloric restriction, cachexia, and psychosocial stress, orchestrating changes in several metabolic processes and behaviors to promote survival. Activation of the ghrelin system could be a viable pharmacological approach to promote food intake and defend against hypoglycemia, body weight loss, depression/anxiety, and death during extreme nutritional and psychological challenges including severe caloric restriction, cachexia, and psychosocial stress.