The current study measured seven feeding responses by non-sulfated cholecystokinin-8 (NS CCK-8) in freely fed adult male Sprague Dawley rats. The peptide (0, 0.5, 1, 3, 5 and 10nmol/kg) was given intraperitoneally (ip) prior to the onset of the dark cycle, and first meal size (MS), second meal size, intermeal interval (IMI) length, satiety ratio (SR = IMI/MS), latency to first meal, duration of first meal, number of meals and 24-hour food intake were measured. We found that NS CCK-8 (0.5 and 1.0nmol/kg) reduced MS, prolonged IMI length and increased SR during the dark cycle. Furthermore, the specific CCK-B receptor antagonist L365, 260 (1 mg/kg, ip) attenuated these responses. These results support a possible role for NS CCK-8 in regulating food intake.
This confirmatory work is aimed to test that the hypothesis that the gastrin releasing peptide (GRP) receptor – the BB2 receptor – is necessary for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by the small and the large forms of GRP in the rat, GRP-10 and GRP-29, and to confirm the sites of action regulating such responses – the vascular bed of the celiac artery (CA, supplying stomach and upper duodenum). To pursue these aims we measured first MS and IMI length in response to GRP-10 and GRP-29 (0, 0.5 nmol/kg) infused in the CA (n=8 rats) and the cranial mesenteric artery (CMA, supplying the small and part of the large intestine, n=8 rats) in near spontaneously free feeding rats pretreated with the BB2 receptor antagonist BW2258U89 (0.1 mg/kg) in the same arteries prior to the onset of the dark cycle. We found that GRP-29, but not GRP-10, infused by the CA reduced MS and prolonged the IMI by decreasing meal latency and meal duration and the BB2 receptor antagonist BW2258U89 infused in the same artery attenuated these responses. These results suggest that the BB2 receptor is necessary for reduction of MS and prolongation of the IMI by exogenous GRP-29, and the vascular bed of the CA, stomach and upper duodenum, contains sites of action regulating these feeding responses.
Two separate experiments were performed to localize the gastrointestinal sites of action regulating meal size (MS), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS) by cholecystokinin (CCK) 8 and 33. Experiment 1: CCK-8 (0, 0.05, 0.15, 0.25 nmol/kg) was infused in the celiac artery (CA, supplies stomach and upper duodenum) or the cranial mesenteric artery (CMA, supplies small and part of the large intestine) prior to the onset of the dark cycle in free feeding, male Sprague Dawley rats and MS (normal rat chow), IMI and SR were recorded. Experiment 2: CCK-33 (0, 0.05, 0.15, 0.25 nmol/kg) were infused in the CA or the CMA, under the same experimental conditions above, and MS, IMI and SR were recorded. Experiment 1 found that CCK-8 reduces MS, prolongs the IMI and increases the SR at sites supplied by both arteries. Experiment 2 found that CCK-33 reduces MS and increases the SR at sites supplied by the CMA. We conclude that in male rats the feeding behaviors evoked by CCK-33, but not CCK-8, are regulated at specific gastrointestinal sites of action.
Background
Roux-en-Y gastric bypass (RYGB) is the most effective method for the treatment of obesity and metabolic disease Roux-en-Y gastric bypass (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 a 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.
Conclusion
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.
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