Disease relevance of Ghrelin

• Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects [1].
• Circulating preprandial ghrelin to obestatin ratio is elevated in human obesity [2].
• We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes [3].
• Our recent study has shown that plasma levels of ghrelin were significantly reduced in sepsis; and ghrelin administration improved organ perfusion and function [4].
• The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I [5].
• Long-term administration of ghrelin kept aged mice with low body weight and low adiposity [6].
• These results demonstrate the therapeutic benefits of ghrelin for impeding the pathogenesis of pulmonary hypertension and right ventricular hypertrophy, particularly in subjects prone to CH (e.g. pulmonary disorders) [7].
• We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects [8].

Associations of Ghrelin with other chemical compounds

• Both insulin and ghrelin are now known to enhance hippocampal memory processes; in addition, insulin acts to increase local hippocampal metabolism and regulate synaptic plasticity, while administration of ghrelin has been shown to promote dendritic spine synaptic formation and to increase anxiety [9].
• Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin) vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs. 6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose production was similar [10].
• Ghrelin inhibits insulin release in mice, rats and humans [11].
• Ghrelin stimulated cortisol and GH secretion, whereas astressin B pretreatment prevented the cortisol, but not the GH, release [12].

Gene context of Ghrelin

• Hence, in C57BL/6J male mice, aging is not associated with changes in circulating ghrelin levels or changes in ghrelin receptor expression in the pituitary gland and brain [13].
• Chronic social defeat stress, a rodent model of depression, persistently increased ghrelin levels, whereas growth hormone secretagogue receptor (Ghsr) null mice showed increased deleterious effects of chronic defeat [14].
• Treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions [15].

References