Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease

Abstract

Gastroesophageal reflux disease (GERD) is often associated with decreased upper gastrointestinal motility, and ghrelin is an appetite-stimulating hormone known to increase gastrointestinal motility. We investigated whether ghrelin signaling is impaired in rats with GERD and studied its involvement in upper gastrointestinal motility. GERD was induced surgically in Wistar rats. Rats were injected intravenously with ghrelin (3 nmol/ rat), after which gastric emptying, food intake, gastroduodenal motility, and growth hormone (GH) release were investigated. Furthermore, plasma ghrelin levels and the expression of ghrelin-related genes in the stomach and hypothalamus were examined. In addition, we administered ghrelin to GERD rats treated with rikkunshito, a Kampo medicine, and examined its effects on gastroduodenal motility. GERD rats showed a considerable decrease in gastric emptying, food intake, and antral motility. Ghrelin administration significantly increased gastric emptying, food intake, and antral and duodenal motility in sham-operated rats, but not in GERD rats. The effect of ghrelin on GH release was also attenuated in GERD rats, which had significantly increased plasma ghrelin levels and expression of orexigenic neuropeptide Y/agouti-related peptide mRNA in the hypothalamus. The number of ghrelin-positive cells in the gastric body decreased in GERD rats, but the expression of gastric preproghrelin and GH secretagogue receptor mRNA was not affected. However, when ghrelin was exogenously administered to GERD rats treated with rikkunshito, a significant increase in antral motility was observed. These results suggest that gastrointestinal dysmotility is associated with impaired ghrelin signaling in GERD rats and that rikkunshito restores gastrointestinal motility by improving the ghrelin response. gastric emptying; food intake; growth hormone; rikkunshito

Р. Leu72met Mutation of Ghrelin GHRL Gene in Children With Gastroesophageal Reflux Disease

“…Ghrelin is expressed by GHRL gene, several SNP are informed for it. In literature is actively studied the SNP allele polymorphism with obesity [10,11], food behavior disorders [12] and metabolism disturbances [13], and also with gastric acid secretion [14] and fast stomach emptying [15,16]. Mutations in this gene can cause low levels of ghrelin, registered at obesity [17].…”

The Effect of Laparoscopic Sleeve Gastrectomy with Concomitant Hiatal Hernia Repair on Gastroesophageal Reflux Disease in the Morbidly Obese

“…Disruption of the cardiac sling fibers have also been correlated with a decrease in LES tone. Nahata et al proposed the concept that impaired ghrelin signaling as predisposing patients to GERD after sleeve gastrectomy [29]. The routine repair of small hiatal hernias may contribute to LES dysfunction by disrupting the normal anatomical barriers to reflux in order to perform the repair.…”

Changes in Ghrelin-Related Factors in Gastroesophageal Reflux Disease in Rats

“…Ghrelin increases food intake and suppresses energy expenditure [3, 11]. In our previous study, we used GERD rats to demonstrate lack of responsiveness through an acute bolus administration of ghrelin (3 nmol/rat) [12]. In comparison with sham-operated rats, the growth hormone secretory effect in GERD rats intravenously administered acyl ghrelin decreased, and acute administration of acyl ghrelin did not suppress the decrease in food intake, gastric emptying, or gastric motility.…”

“…Repeated administration of acyl ghrelin (3 nmol/rat/day) to GERD rats had no effect on food intake or body weight throughout the experiment in this study. We previously demonstrated that acute intravenous administration of acyl ghrelin at a dose of 3 nmol/rat to sham-operated rats increased food intake significantly [12]. In normal rats, administration of ghrelin at a dose of 1.5 nmol/rat also increased food intake significantly [13].…”