Abstract
Performing the Roux-en-Y gastric bypass (RYGBP) in obese Yucatan minipigs provides an opportunity to explore the mechanisms behind the effects of this surgery in controlled environmental and nutritional conditions. We hypothesized that RYGBP in these minipigs would induce changes at multiple levels, as in obese humans. We sought to characterize RYGBP in a diet-induced obese minipig model, compared with a pair-fed sham group. After inducing obesity with an ad libitum high-fat/high-sugar diet, we performed RYGBP (n = 7) or sham surgery (n = 6). Oral glucose tolerance tests (OGTT) were performed before and after surgery. Histological analyses were conducted to compare the alimentary limb at sacrifice with tissue sampled during RYGBP surgery. One death occurred in the RYGBP group at postoperative day (POD) 3. Before sacrifice, weight loss was the same across groups. GLP-1 secretion (OGTT) was significantly higher at 15, 30 and 60 min at POD 7, and at 30 and 60 min at POD 30 in the RYGBP group. Incremental insulin area under the curve increased significantly after RYGBP (p = 0.02). RYGBP induced extensive remodeling of the alimentary limb. Results show that RYGBP can be safely performed in obese minipigs, and changes mimic those observed in humans.
Highlights
Abbreviations RYGBP Roux-en-Y gastric bypass glucagon-like peptide 1 (GLP1) Glucagon-like peptide 1 Oral glucose tolerance tests (OGTT) Oral glucose tolerance test postoperative day (POD) Postoperative day HDL High-density lipoprotein short-chain fatty acids (SCFAs) Short-chain fatty acid standard error of the mean (SEM) Standard error of the mean AUCi Incremental area under the curve
GLP1 is released by L-cells in response to the presence of nutrients in the gut lumen, and some studies have demonstrated that blocking GLP1 receptors with an agonist reduces β-cell glucose sensitivity and insulin secretion after RYGBP6,7
One death occurred in the RYGBP group at postoperative day (POD) 3, owing to a massive septic shock induced by a gastrojejunal leak (Fig. 1A)
Summary
Abbreviations RYGBP Roux-en-Y gastric bypass GLP1 Glucagon-like peptide 1 OGTT Oral glucose tolerance test POD Postoperative day HDL High-density lipoprotein SCFA Short-chain fatty acid SEM Standard error of the mean AUCi Incremental area under the curve. The Roux-en-Y gastric bypass (RYGBP) is one of the most efficient and widespread bariatric surgery techniques for reducing weight and improving obesity-related diseases, especially type-2 diabetes and cardiovascular d isease[4]. In rodents, glucose tolerance after RYGBP has been found to vary according to GLP1 agonist (exendin-4) sensitivity[9]. These studies seem to indicate that GLP1 plays an important role in glucose homeostasis after RYGBP. Some human studies have reported changes in brain signaling induced by obesity and their reversal after RYGBP, but the mechanisms are still unclear[11]. Changes in basal brain metabolism were observed and these changes were similar to those described in obese h umans[14]
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