New Metabolic Influencer on Oxytocin Release: The Ghrelin.

BACKGROUND: The hypothalamic⁻pituitary axis by secreting neuropeptides plays a key role in metabolic homeostasis. In light of the metabolic regulation, oxytocin is a potential neuropeptide for therapies against obesity and related disorders. The aim of our study is to measure ghrelin-induced oxytocin secretion in rats and to detect the changes after administration of ghrelin antagonist. METHODS: Ghrelin was administrated centrally (intracerebroventricular, i.c.v., 1.0, 10.0, and 100.0 pmol) or systemically (intravenous, i.v., 1.0, and 10.0 nmol). [d-Lys³]-GHRP-6 ghrelin antagonist was injected 15 min before ghrelin injection in a dose of 10.0 pmol i.c.v. and 10.0 nmol i.v. RESULTS: Either i.c.v. or i.v. administration of ghrelin dose-dependently increased the plasma oxytocin concentration. Following pretreatment with the ghrelin antagonist [d-Lys³]-GHRP-6, the high plasma oxytocin level induced by ghrelin was significantly reduced. CONCLUSION: The results indicate that the release of oxytocin is influenced directly by the ghrelin system. Examination of the mechanism of ghrelin-induced oxytocin secretion is a new horizon for potential therapeutic options.

Ghrelin Induces Place Preference for Social Interaction in the Larger Peer of a Male Rat Pair.

Social interaction is important for survival in most social species including humans. To ensure social activities, individuals experience reward from social interaction, generating a powerfully reinforcing process. Here we hypothesized that reward from social interaction in a juvenile male rat pair may be enhanced by ghrelin, a circulating hormone that has been shown to enhance reward from other natural (e.g. food, sex) as well as artificial reinforcers (e.g. alcohol and other drugs of abuse). To this end, we assessed the impact of ghrelin and a ghrelin antagonist on preference for a chamber previously paired to the presence of a social partner in a conditioned place preference paradigm. We found that ghrelin increased and a ghrelin antagonist decreased preference for social interaction, but only in the heavier partner in a social pair. In addition, we found that administered ghrelin induced a positive association between preference for social interaction and body weight difference within socially interacting pairs, where larger ghrelin treated rats preferred social interaction, whereas smaller ghrelin treated rats avoided it, which raises the question if ghrelin could have a role in implementing social hierarchies in rats. In summary, we conclude that ghrelin signaling increases the reward from social interaction in a manner that reflects the degree of divergence in body weight between the social pair.

Novel Regulator of Acylated Ghrelin, CF801, Reduces Weight Gain, Rebound Feeding after a Fast, and Adiposity in Mice.

Ghrelin is a 28 amino acid hormonal peptide that is intimately related to the regulation of food intake and body weight. Once secreted, ghrelin binds to the growth hormone secretagogue receptor-1a, the only known receptor for ghrelin and is capable of activating a number of signaling cascades, ultimately resulting in an increase in food intake and adiposity. Because ghrelin has been linked to overeating and the development of obesity, a number of pharmacological interventions have been generated in order to interfere with either the activation of ghrelin or interrupting ghrelin signaling as a means to reducing appetite and decrease weight gain. Here, we present a novel peptide, CF801, capable of reducing circulating acylated ghrelin levels and subsequent body weight gain and adiposity. To this end, we show that IP administration of CF801 is sufficient to reduce circulating plasma acylated ghrelin levels. Acutely, intraperitoneal injections of CF801 resulted in decreased rebound feeding after an overnight fast. When delivered chronically, they decreased weight gain and adiposity without affecting caloric intake. CF801, however, did cause a change in diet preference, decreasing preference for a high-fat diet and increasing preference for regular chow diet. Given the complexity of ghrelin receptor function, we propose that CF801, along with other compounds that regulate ghrelin secretion, may prove to be a beneficial tool in the study of the ghrelin system, and potential targets for ghrelin-based obesity treatments without altering the function of ghrelin receptors.