Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents

Abstract

Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake. However, more than 7 yr after its discovery, the role of endogenous ghrelin remains elusive. Recently, a second peptide, obestatin, also generated from proteolytic cleavage of preproghrelin has been identified. This peptide inhibits food intake and gastrointestinal motility but does not modify in vitro GH release from pituitary cells. In this study, we have reinvestigated obestatin functions by measuring plasma ghrelin and obestatin levels in a period of spontaneous feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous obestatin per se did not modify food intake in fasted and fed mice. However, it inhibited ghrelin orexigenic effect that were evident in fed mice only. The effects of obestatin on GH secretion were monitored in superfused pituitary explants and in freely moving rats. Obestatin was only effective in vivo to inhibit ghrelin stimulation of GH levels. Finally, the relationship between octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative blood sampling every 20 min during 6 h in freely moving adult male rats. The half-life of exogenous obestatin (10 microg iv) in plasma was about 22 min. Plasma obestatin levels exhibited an ultradian pulsatility with a frequency slightly lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not strictly correlated. In conclusion, these results show that obestatin, like ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin can modulate exogenous ghrelin action. It remains to be determined whether obestatin modulates endogenous ghrelin actions.

Proghrelin peptides: Desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin

“…Plasma desacyl ghrelin levels are typically 5-10-fold higher than acyl ghrelin in rat, mouse and man (desacyl ghrelin levels in rodents ranging between 150-600 pmol/l while acyl ghrelin levels range between 10-50 pmol/l) (8,10). Obestatin levels are also higher than acyl ghrelin levels, ranging between 100-800 pmol/l (9,21,56). The circulating concentrations of acyl ghrelin and desacyl ghrelin are known to vary with the prandial state, being 3-10 times higher in fasted than in fed animals (1,4,7-10).…”

Circulating obestatin levels and the ghrelin/obestatin ratio in obese women

“…Obestatin was also thought to display effects opposite to those of ghrelin (1,6). However, recent studies did not support a role for obestatin either in the regulation of food intake or on body weight, energy expenditure control or growth hormone secretion (7)(8)(9).…”

Obestatin is associated to muscle strength, functional capacity and cognitive status in old women

“…Its participation in the regulation of energetic homeostasis in humans has been suggested, and initial data pointed towards the idea that obestatin was driving an anorexigenic message in contraposition to the orexigenic effect of ghrelin. However, various recent studies have shown conflictive results regarding this (Nakahara et al 2008;Nogueiras et al 2007;Zhang et al 2005;Zizzari et al 2007). In a recent study, we found that obestatin was not associated to weight loss or diminished appetite or decreased eating behaviour frequently observed in the ageing phenomenon and referred to as anorexia of aged people (Mora et al 2012a).…”