Balance in Ghrelin and Leptin Plasma Levels in Anorexia Nervosa Patients and Constitutionally Thin Women

Abstract

Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects in both rodents and humans. As the endogenous peptide appears directly related to feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients before and after renutrition and in constitutionally thin subjects with body mass indexes (BMIs) equivalent to those of AN women but with no abnormal feeding behavior. The relationships between plasma ghrelin levels and other neuroendocrine and nutritional parameters, such as GH, leptin, T3, and cortisol, were also investigated. In AN patients, morning fasting plasma ghrelin levels were doubled compared with levels in controls, constitutionally thin subjects, and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and cortisol levels determined every 4 h were significantly increased, whereas 24-h plasma leptin levels were decreased in AN patients compared with controls and constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to control values in AN patients after renutrition. Constitutionally thin subjects displayed intermediate 24-h plasma ghrelin and leptin levels, significantly different from controls and AN patients, whereas GH and cortisol were not modified. Ghrelin was negatively correlated with BMI, leptin, and T(3) in controls, constitutionally thin subjects, and AN patients, whereas no correlation was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI or T3 were still correlated after renutrition, suggesting that ghrelin is also a good nutritional indicator. Basal and GHRH-stimulated GH release were significantly increased in AN patients only. In conclusion, ghrelin is increased in AN and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status. Even though endogenous ghrelin is not strictly correlated with basal GH secretion, it may be involved in the magnitude of GHRH-induced GH release in AN patients.

Serum Ghrelin, IGF-I and IGFBP-3 Levels In Children with Normal Variant Short Stature

“…Ghrelin, as is very well known, has profound orexigenic and adipogenic properties functioning as a signal for the hypothalamus when an increase in metabolic substrates is needed [15][16][17][18]28]. Therefore, it seems to be logic that ghrelin levels might be elevated in our patients, especially in the CDG group as an adaptive mechanism to lowered body weight, as seen in patients with anorexia nervosa and in obese subjects who lose weight with diet [29,30]. This suggestion cannot solely explain the elevated ghrelin levels in our patients because of two reasons; first, although our FSS group had lower body weight compared to controls, the difference did not reach statistical significance so that there should be another reason for the elevated ghrelin levels in our FSS group; second, in the multiple regression model, body weight was not the only predictor of serum ghrelin levels, with height SDS being the other independent determinant.…”

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: Association with subtype, body-mass index, severity and age of onset

“…Plasma ghrelin levels are highly elevated in patients with AN and return to normal after weight gain (Otto et al, 2001;Tolle et al, 2003). It has been shown that the bingeeating/purging subtype group had higher levels than the restricting subtype and still had higher levels than the controls after weight gain (Tanaka et al, 2004).…”

La ghréline, un exemple saisissant de pléïotropie des peptides neuroendocriniens

“…Chez l'homme, en l'absence d'indice temporel ou de nourriture, l'augmentation de ghréline est bien corrélée à la sensation de faim, ce qui renforce l'hypothèse du rôle orexigène du peptide [40]. Il existe une corrélation négative entre l'indice de masse corporelle et les concentrations plasmatiques de ghréline à jeun : l'amaigrissement chez le sujet obèse s'accompagne d'une augmentation des niveaux de ghréline [41], tandis que l'inverse est observé avec la prise de poids en cas d'anorexie nerveuse [42]. Les patients insulinorésistants ou souffrant d'un diabète de type 2 présentent également de faibles concentrations de ghréline cir- Effets paracrines sur la prolifération Testostérone concentrations de ghréline sont abaissées dans tous les cas d'obésité humaine d'origine génétique (déficience en leptine, mutations du récepteur de la leptine ou du récepteur 4 de la mélanocortine, MC4), ou hypothalamique (craniopharyngiomes), elles sont particulièrement élevées dans le syndrome de Prader-Willi [46], du même ordre de grandeur qu'au cours de l'anorexie nerveuse : il a été proposé que ces concentrations très élevées de ghréline pouvaient contribuer à l'hyperphagie sévère des enfants atteints.…”