Roux-en-Y gastric bypass augments the feeding responses evoked by gastrin-releasing peptides

Abstract

Background: Roux-en-Y gastric bypass (RYGB) is the most effective method for the treatment of obesity, and metabolic disease RYGB may reduce body weight by altering the feeding responses evoked by the short-term satiety peptides.

Materials and methods: Here, we measured meal size (MS, chow), intermeal interval (IMI) length, and satiety ratio (SR, IMI/MS; food consumed per a unit of time) by the small and the large forms of gastrin-releasing peptide (GRP) in rats, GRP-10 and GRP-29 (0, 0.1, 0.5 nmol/kg) infused in the celiac artery (CA, supplies stomach and upper duodenum) and the cranial mesenteric artery (CMA, supplies small and large intestine) in an RYGB rat model.

Results: GRP-10 reduced MS, prolonged the IMI, and increased the SR only in the RYGB group, whereas GRP-29 evoked these responses by both routes and in both groups.

Conclusions: The RYGB procedure augments the feeding responses evoked by exogenous GRP, possibly by decreasing total food intake, increasing latency to the first meal, decreasing number of meals or altering the sites of action regulating MS and IMI length by the two peptides.

Keywords: Celiac artery; Cranial mesenteric artery; Food intake; GRP; Roux-en-Y.

Figure 1. Roux-en-Y gastric bypass

The surgery is performed in two steps. First, a gastric pouch is created by removing the fundus and closing the antrum. Second, the jejunum is cut 40 cm distal to the pyloric sphincter and (A) is anastomosed (end to side) to the newly created gastric pouch (A′), and the proximal end of the jejunum (B) is anastomosed by an end to side anastomosis with the jejunum 10 cm distal to the original cut.

Figure 2. Effect of gastrin releasing peptide-10 and 29 on the first meal size, intermeal interval length and satiety ratio in Roux-en-Y gastric bypass rats

Gastrin releasing peptide-10 and 29(GRP-10, 0, 0.1, 0.5 nmol/kg, GRP-29, 0, 0.1, 0.5 nmol/kg) was infused in the celiac artery (CA) and cranial mesenteric artery (CMA) in sham-operated rats and in Roux-en-Y gastric bypass (RYGB) –operated, near spontaneously free feeding rats prior to the onset of the dark cycle and the first meal size (MS, normal rat chow), intermeal interval (IMI) and satiety ratio (SR = IMI/MS) were determined. GRP-10 lowered meal size, prolonged the IMI was prolonged and increased the SR was increased in the RYGB group more than in the sham group (‡, p<0.05). GRP-29 given by both routes reduced MS relative to saline vehicle (*, p<0.05) and more so by the 0.5 nmol/kg dose compared to the 0.1 nmol/kg dose (**, p<0.05). In the RYGB group both doses of GRP-29 and by both routes prolonged the IMI relative to saline vehicle (*, p<0.05), and there was more prolongation by the 0.5nmol/kg in the CMA than in the sham group (‡, p<0.05). Only GRP-29 given by the CA prolonged the IMI in the sham group (*, p<0.05). GRP-29 0.1 and 0.5nmol/kg increased the SR relative to saline control (*, p<0.05) and GRP-29 0.5nmol/kg increased it more than 0.1nmol/kg (**, p<0.05.).

Figure 3. Effect of gastrin releasing peptide-10 and 29 on various feeding behaviors in Roux-en-Y gastric bypass rats

Gastrin releasing peptide-10 and 29(GRP-10, 0, 0.1, 0.5 nmol/kg, GRP-29, 0, 0.1, 0.5 nmol/kg) was infused in the celiac artery (CA) and cranial mesenteric artery (CMA) in sham-operated and in Roux-en-Y gastric bypass (RYGB) –operated, near spontaneously free feeding rats prior to the onset of the dark cycle and total intake (24-hr intake, chow), latency to first meal and duration of first meal were recorded. GRP-10 reduced total intake relative to saline vehicle (*, p<0.05) and there was more reduction in total intake and prolongation in the latency to the first meal in the RYGB group than the sham group (‡, p<0.05). Both doses of GRP-29 reduced total intake in both groups relative to saline control (*, p<0.05) and 0.5nmol/kg reduced it more than 0.1nmol/kg (**, p<0.001). In both groups and by both routes GRP-29 increased the latency to the first meal relative to saline control (*, p<0.05) and more so in the RYGB group than the sham group (‡, p<0.05). GRP-29 0.5nmol/kg given by the CA route increased the latency to the first meal more than 0.1nmol/kg in the sham group (**, p<0.05). Both GRP-29 0.1 and 0.5nmol/kg reduced the duration of the first meal relative to saline vehicle (*, p<0.05).

Figure 4. Effect of gastrin releasing peptide-10 and -29 on the number of meals in Roux-en-Y gastric bypass rats

Gastrin releasing peptide-10 and -29(GRP-10, 0, 0.1, 0.5 nmol/kg, GRP-29, 0, 0.1, 0.5 nmol/kg) were infused individually in the celiac artery (CA) and cranial mesenteric artery (CMA) in sham-operated and in Roux-en-Y gastric bypass (RYGB) –operated, near spontaneously free feeding rats prior to the onset of the dark cycle and the number of meals were counted during the dark cycle. The number of meals in the RYGB group was less than the number of meals in the sham group (‡, p<0.05) in those rats given GRP-10.The number of meals were reduced by GRP-29 relative to saline vehicle (*, p<0.05) and there was more reduction in the RYGB group (‡, p<0.05).

Figure 5. Distribution of Gastrin Releasing Peptide Receptors

This schematic presentation indicates the distribution GRP in the gut. The highest secretion of GRP is shown to be primarily in the distal stomach, distal duodenum, proximal stomach and intermediately secreted in the colon, moderately secreted in the jejunum esophagus, pyloric sphincter, proximal duodenum, ileum and rectum (3 dots), and the lowest secretion was in the cecum.