Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats

Abstract

Ghrelin, a 28-amino-acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. We have reported previously that central or peripheral administration of ghrelin stimulates food intake, and the secretion of GH and gastric acid in rats. In the present study, we investigated how much endogenous centrally released ghrelin is involved in the control of food intake and body weight gain. We also examined the profile of ghrelin secretion from the stomach by RIA using two kinds of anti-ghrelin antiserum, one raised against the N-terminal ([Cys 12 ]-ghrelin[1-11]) region and one raised against the C-terminal ([Cys 0 ]-ghrelin [13-28]) region of the peptide. The former antibody recognizes specifically ghrelin with n-octanoylated Ser 3 (acyl ghrelin), and does not recognize des-acyl ghrelin. The latter also recognizes des-acyl ghrelin (i.e. total ghrelin). Intracerebroventricular treatment with the antighrelin antiserum against the N-terminal region twice a day for 5 days decreased significantly both daily food intake and body weight. Des-acyl ghrelin levels were significantly higher in the gastric vein than in the trunk. Either fasting for 12 h, administration of gastrin or cholecystokinin resulted in increase of both acyl and des-acyl ghrelin levels. The ghrelin levels exhibited a diurnal pattern, with the bimodal peaks occurring before dark and light periods. These two peaks were consistent with maximum and minimum volumes of gastric content respectively. These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.

Bravo capsule system optimizes intragastric pH monitoring over prolonged time: Effects of ghrelin on gastric acid and hormone secretion in the rat

“…Our results using the Bravo system, with an increase of intragastric pH during 1 wk after three times daily, administration of ghrelin, are in accordance with earlier studies [19,22] , but at variance with another [23] . This may be explained by the fact that different methods for studying gastric acid secretion have been employed, some of which are dependent on gastric motility for the emptying of gastric secretions through the fistula.…”

“…This might be due to the fact that motility was stimulated by a continuous infusion of the hormone, whereas the pH effect was brought about by repeated injections of ghrelin, a form of administration that is considered less liable to desensitization effects. As ghrelin not only increases intragastric pH, but also stimulates gastric emptying in rodents [22,23,25,26] . This may be an erroneous factor in determining acid secretion using the fistula method.…”

Vagal stimulation exaggerates the inhibitory ghrelin response to oral fat in humans

“…Rodent studies examining the relationship between vagal activity and fasting ghrelin secretion have provided conflicting data. Electrical stimulation of the vagus nerve in fasting rodents caused an increase in circulating concentrations of ghrelin (Murakami et al 2002), whereas a separate study showed an elevation in ghrelin concentrations following vagotomy (Lee et al 2002). However, it must be noted that the measurements of ghrelin were made 14 days after vagotomy, representing long-term changes, rather than the acute changes currently observed.…”

“…The vagus nerve has been shown to be intrinsically linked to both ghrelin regulation (Lee et al 2002) and action (Masuda et al 2000). Vagotomy elevates plasma ghrelin significantly (Lee et al 2002), whereas electrical stimulation of the vagus nerve tends to decrease ghrelin in rats (Murakami et al 2002). Habitual purging in patients with bulimia nervosa has provided indirect evidence of a potential link between vagal activity and fasting ghrelin concentrations.…”

Interactions of ghrelin signaling pathways with the GH neuroendocrine axis: a new and experimentally tested model

“…In the work of Tolle et al (2002), the small variation of ghrelin would be difficult to associate with oscillatory behavior (a day-night rhythm cannot be attributed to the measured profiles). Murakami et al (2002) determined an apparent diurnal rhythm of ghrelin in the blood plasma, revealing peaks just before the light-on and light-off transitions. However, but for these two peaks, ghrelin is almost constant in these profiles.…”