Obestatin acts in brain to inhibit thirst

Abstract

Derived from the same prohormone, obestatin has been reported to exert effects on food intake that oppose those of ghrelin. The obestatin receptor GPR39 is present in brain and pituitary gland. Since the gene encoding those two peptides is expressed also in those tissues, we examined further the possible actions of obestatin in vivo and in vitro. Intracerebroventricular administration of obestatin inhibited water drinking in ad libitum-fed and -watered rats, and in food-and water-deprived animals. The effects on water drinking preceded and were more pronounced than any effect on food intake, and did not appear to be the result of altered locomotor/behavioral activity. In addition, obestatin inhibited ANG II-induced water drinking in animals provided free access to water and food. Current-clamp recordings from cultured, subfornical organ neurons revealed significant effects of the peptide on membrane potential, suggesting this as a potential site of action. In pituitary cell cultures, log molar concentrations of obestatin ranging from 1.0 pM to 100 nM failed to alter basal growth hormone (GH) secretion. In addition, 100 nM obestatin failed to interfere with the stimulation of GH secretion by GH-releasing hormone or ghrelin and did not alter the inhibition by somatostatin in vitro. We conclude that obestatin does not act in pituitary gland to regulate GH secretion but may act in brain to alter thirst mechanisms. Importantly, in rats the effects of obestatin on food intake may be secondary to an action of the peptide to inhibit water drinking.

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

“…However, obestatin is produced by the gastrointestinal tract, the peripheral obestatin might cross the bloodbrain barrier and enter the hippocampus and amygdala and by activating these brain regions they may modulate the behavior of rodents [13]. We administrated obestatin centrally in harmony with previous studies [38][39][40][41].…”

Ghrelin Gene Products in Acute and Chronic Inflammation

“…Nevertheless, obestatin has several biological activities, including protective effects on the cardiovascular system (Agnew et al 2012;Alloatti et al 2010;Aragno et al 2012), promotion of adipocytes survival, differentiation, and metabolism Gurriarán-Rodríguez et al 2011;Miegueu et al 2011;Pruszynska-Oszmalek et al 2013), induction of myoblasts differentiation and promotion of skeletal muscle regeneration (Gurriarán-Rodríguez et al 2012), inhibition of pancreatic b-cell and islets apoptosis, stimulation of glucose-stimulated insulin secretion in both normal and diabetic animal models, and enhancement of functional bcell generation from pancreatic precursor cells (Baragli et al 2013;Granata et al 2008Granata et al , 2010. Notably by an evolutionary point of view, while ghrelin is mainly involved in food intake, obestatin has an inhibitory effect on water drinking by acting on mechanisms involved in the thirst (Samson et al 2007) and decreases vasopressin concentration in plasma (Samson et al 2008).…”

Obestatin Promotes Survival of Pancreatic β-Cells and Human Islets and Induces Expression of Genes Involved in the Regulation of β-Cell Mass and Function

“…Moreover, it was found to counteract ghrelin stimulatory effects on these end points (1,9) and to inhibit ghrelininduced growth hormone secretion in vivo (9) but not in vitro (10), suggesting that it would serve as a physiological opponent of ghrelin. However, a number of studies failed to confirm obestatin anorexigenic effects (11-14), and besides not being the cognate ligand for GPR39, its biological actions seem to be a controversial issue.Obestatin has been reported to inhibit thirst and to influence memory, anxiety, and sleep via central activities (10,15,16). At the cellular level, it stimulates proliferation of human retinal cells (17) but has no effect on murine cardiomyocyte and condrocyte viability (18,19).…”