Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats

Abstract

Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food intake and neuronal activity (c-Fos) in the arcuate nucleus in non-fasted rats. Ghrelin (13 μg/kg) significantly increased food intake within the first 30 min post injection. Desacyl ghrelin at 64 and 127 μg/kg injected simultaneously with ghrelin abolished the stimulatory effect of ghrelin on food intake. Desacyl ghrelin alone at both doses did not alter food intake. Both doses of desacyl ghrelin injected separately in the light phase had no effects on food intake when rats were fasted for 12 h. Ghrelin and desacyl ghrelin (64 μg/kg) injected alone increased the number of Fos positive neurons in the arcuate nucleus compared to vehicle. The effect on neuronal activity induced by ghrelin was significantly reduced when injected simultaneously with desacyl ghrelin. Double labeling revealed that nesfatin-1 immunoreactive neurons in the arcuate nucleus are activated by simultaneous injection of ghrelin and desacyl ghrelin. These results suggest that desacyl ghrelin suppresses ghrelin-induced food intake by curbing ghrelininduced increased neuronal activity in the arcuate nucleus and recruiting nesfatin-1 immunopositive neurons.

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

“…Another population to investigate might be patients with the metabolic syndrome, especially since reports suggest that diabetes and obesity are linked with a relative DAG deficiency or an increased AG:DAG ratio (20,21,22,23).…”

“…Another indication of the importance of DAG levels as a potential physiological inhibitor of AG action has been reported already by the above-mentioned studies of transgenic mice overexpressing DAG (32,33,37), which were lighter and shorter compared with controls. In another example of its antagonistic effects, DAG was found to suppress AG-induced neuronal activity in the arcuate nucleus of rats, thus suppressing the induction of food intake by AG (21).…”

Ghrelin Gene Products in Acute and Chronic Inflammation

“…Unacylated ghrelin participates also in the regulation of food intake and adipogenesis through mechanisms not fully elucidated, but very likely independent of GHS-R1a (Asakawa et al 2005;Inhoff et al 2008;Toshinai et al 2006).…”

Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

“…This suggests the presence of very high serum levels of desacyl ghrelin in our patients, even if we could not definitely exclude the presence of circulating degradation products of mature ghrelin peptides. Several mechanisms may therefore be hypothesized to explain the absence of functional consequences of ghrelin overproduction in our patients, such as: i) competition between desacyl ghrelin and acyl ghrelin, as previously suggested on experimental grounds (4,(18)(19)(20)(21) and ii) interference with other mechanisms contributing to the regulation of appetite and the induction of cachexia in patients with advanced cancer, such as inflammatory cytokines and adipokines. The limited amount of tumor tissue available for study in our patients and the absence of frozen tissue prevented the possibility to analyze in depth the expression and metabolism of ghrelin in tumor tissues and to evaluate the expression of its specific receptors.…”

“…Ghrelin exists in two major forms: n-octanoyl-ghrelin (acyl ghrelin) and des-n-octanoyl ghrelin (desacyl ghrelin). Octanoylation, mediated by a specific enzyme, ghrelin O-acyltransferase (GOAT), is essential for the binding of ghrelin to GHS-R1a; however, although desacyl ghrelin is not able to bind to GHS-R1a, it may have some biological activities and may even be an antagonist of the orexigenic effects of acyl ghrelin (4).…”