Gastric Ghrelin Secretion Research Articles

Growth hormone and somatostatin directly inhibit gastric ghrelin secretion. An in vitro organ culture system

Ghrelin is a 28-amino-acid hormone produced mainly by the stomach which strongly promotes food intake. It is the only known peripheral orexigenic hormone that induces the release of GH. Ghrelin has been proposed as a link between the enteric system and central regulation of energy balance and growth. Although it has recently been the focus of extensive study, the secretion mechanism is not yet well characterized. The aim of this study was to test the direct effect of hormones from the somatotropic axis on ghrelin release directly from the stomach. To this end, an organ culture model of gastric tissue explants from rat donors was used. These stomach explants were incubated in 6 well plates for 1, 2, and 3 h after treatment with either GH, GHRH, SS or IGF-I, all them at 10(-6) M. After incubation, the medium was collected and the amount of ghrelin secreted by the gastric tissue was measured by radioimmunoassay. It was observed that GH and SS significantly decreased gastric ghrelin secretion, while GHRH and IGF-1 had no effect on the present model. These results would confirm the capacity of GH and SS to act directly upon gastric level, inhibiting ghrelin secretion in vitro.

The autonomic nervous system regulates gastric ghrelin secretion in rats

Plasma ghrelin levels are responsive to short- and long-term nutrient fluctuation, but the mechanisms of its regulation are largely unknown. To explore the role of the autonomic nervous system in the regulation of ghrelin secretion, we measured plasma ghrelin levels after administration of cholinergic and adrenergic agents in rats under normally fed and 48-h fasting conditions. To assess the short- and long-term effects of vagotomy on ghrelin secretion, plasma ghrelin levels and stomach ghrelin levels and gene expressions were measured in rats subjected to fed or fasting. Additionally, we investigated whether plasma ghrelin levels were affected by the anorexigenic gastrointestinal peptides cholecystokinin and somatostatin. In the pharmacological study, plasma ghrelin levels were increased by a muscarinic agonist, an α-adrenergic antagonist, and a β-adrenergic agonist, and decreased by a muscarinic antagonist and an α-adrenergic agonist. Vagotomy inhibited ghrelin secretion acutely, but promoted ghrelin release from the stomach at later time points. Stomach ghrelin mRNA levels were unchanged after fasting, but were significantly upregulated in vagotomized rats. The change of plasma ghrelin levels in nutrient fluctuation was independent of the endogenous effects of cholecystokinin and somatostatin. This study demonstrates that stomach ghrelin secretion is modulated by both the cholinergic and adrenergic arms of the autonomic nervous system. The dissociation between the short- and long-term effects of vagotomy on plasma ghrelin level indicates that an additional neural control mechanism might be involved in the regulation of ghrelin secretion.

Sensory Stimuli Directly Acting at the Central Nervous System Regulate Gastric Ghrelin Secretion. An ex Vivo Organ Culture Study

Ghrelin, a novel gastrointestinal hormone involved in GH regulation, has been postulated as a relevant orexigenic peptide released by splanchnic tissues. Descriptive studies have shown that plasma ghrelin levels increase in states of negative energy balance or fasting, while decreasing in obesity and after feeding. In the present study, a novel organ-culture model of gastric tissue explants obtained from rat donors has been validated for ex vivo experiments. Fasting induced gastric ghrelin release as well as ghrelin mRNA expression that were reflected in plasma. Interestingly, those changes were fully reverted by 15 min of refeeding before stomach extraction. Unexpectedly, when animals were allowed 15 min before explant extraction to see or smell, but not eat, the food (tease feeding), ghrelin secretion was suppressed just like in gastric explants from refed animals. This effect was blocked when the animals were subjected to surgical vagotomy or treated with atropine sulphate. In conclusion, gastric explants were a suitable model for testing ghrelin mechanism of secretion in vitro, and they were found to maintain memory of the previously received signals. Similar to feeding, tease feeding resulted in suppression of ghrelin discharge by explants.

Serum Ghrelin Levels and Risk of Subsequent Adenocarcinoma of the Esophagus

Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux. We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls). A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR=0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI>or=25, P value for interaction=0.09). The effects of H. pylori and ghrelin were independent. Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.

Effects of Intragastric Balloon on Gastric Emptying and Plasma Ghrelin Levels in Non-morbid Obese Patients

Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying and ghrelin secretion in non-morbid obese patients. 17 patients were included in the study, with mean BMI of 34.4 (range 30.1-40.0). The balloon was inserted under general anaesthesia and endoscopic control, inflated with 600 ml saline, and removed 6 months later. Body weight and gastric emptying (13C-octanoic acid breath test) were monitored while the balloon was in place and 1 month after removal. Ghrelin levels were measured just before balloon insertion and removal. Mean weight loss was 8.7 kg (range 0-21). Gastric emptying rates were significantly decreased with the balloon in place, and returned to pre-implantation values after balloon removal. Plasma ghrelin levels were significantly decreased (95% CI: -3.8 to -20.7 ng/ml), despite concomitant weight loss. Weight reduction was not correlated to the effect of the balloon on gastric emptying, but was significantly correlated to the ghrelin variations (r=0.668, 95% CI: 0.212-0.885). Gastric emptying rates and plasma ghrelin levels are decreased in the presence of intragastric balloon. Weight loss induced by the intragastric balloon is related to ghrelin variations, but not to gastric emptying. Ghrelin inhibition may explain part of the effect of the balloon on satiety.

Direct Effect of Leptin on Gastric Ghrelin Secretion

Ghrelin is an orexigenic hormone of gastric origin, and contributes to food intake and body weight regulation [1] [2]. Its postprandial secretion is attenuated by carbohydrate-rich meals [3] [4], while carbohydrate-poor food stimulates ghrelin release [5]. Gastrointestinal factors such as gastrin, somatostatin, or GLP-1 are good candidates for ghrelin inhibitors [6]. Also, there is solid evidence that insulin is a powerful inhibitor of ghrelin release in vivo [7] [8] and in vitro [6].

Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans

Objectives: Ghrelin is produced and secreted by the stomach promoting appetite and food intake and was identified as an endogenous ligand for the growth hormone secretagogue-receptor. A gastro-hypophyseal feedback loop seems to regulate gastric ghrelin secretion transducing changes in food intake to CNS in order to regulate energy homeostasis. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. The aim of our study was to investigate ghrelin levels with and without elevated glucocorticoid levels from either endogenous or exogenous origin.

Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats.

The novel gastric hormone ghrelin has recently been identified as an important modulator of energy homeostasis. Leptin-responsive hypothalamic neuropeptide Y/Agouti-related protein neurons are believed to mediate afferent ghrelin signals. Little is known, however, about ghrelin-induced efferent signals. We therefore investigated if hypothalamic-pituitary axes have a role in transferring ghrelin-induced changes of energy balance to the periphery. We subcutaneously injected hypophysectomized, as well as adrenalectomized, thyroidectomized, and sham-operated control rats with GH secretagogues [ghrelin, growth hormone (GH)-releasing peptide] for 1 week. Body weight, food intake, and body composition (chemical carcass analysis) were analyzed and compared with vehicle-treated controls. In addition, we quantified circulating levels of endogenous ghrelin in hypophysectomized and GH-treated normal rats. GH-secretagogue treatment of sham-operated control rats dose-proportionally increased food intake, body weight, and fat mass compared with vehicle-injected controls (p < 0.01). These effects, however, were not observed in ghrelin-treated hypophysectomized, thyroidectomized, or adrenalectomized rats, indicating an essential role for the pituitary axis in ghrelin-induced adiposity. Circulating levels of endogenous ghrelin were reduced by administration of GH in normal rats and were about 3-fold higher in hypophysectomized rats (n = 20, p = 0.001), suggesting a regulatory feedback loop involving the stomach and the pituitary to regulate gastric ghrelin secretion. According to these results, the endocrine pituitary is mediating ghrelin-induced changes toward a positive energy balance and is involved in the regulation of ghrelin secretion through a gastro-hypophyseal feedback loop.