Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restriction

Abstract

Background The effects of gastric bypass surgery on the secretion of the anorexogenic gut-derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), independent of caloric restriction and due to different dietary macronutrients, is not well-characterized. This study examines the effects of a mixed-nutrient or high-fat liquid meal on the postprandial stimulation of GLP-1 and PYY following gastric bypass or equivalent hypocaloric diet. Methods Total PYY and active GLP-1 were measured fasting and at multiple points after standardized mixed-nutrient and high-fat liquid meals in two matched groups of obese subjects. The meal stimulation tests were performed before and 14.6±3.3 days after gastric bypass (GBP, n=10) and before and after a 7-day hypocaloric liquid diet matching the post-GBP diet (Control, n=10). Results Mixed-nutrient and high-fat postprandial GLP-1 levels increased following GBP (mixed-nutrient peak: 85.0±28.6 pg/ml to 323±51 pg/ml, p<0.01; high-fat peak: 81.8±9.6 pg/ml to 278±49 pg/ml, p<0.01), but not after diet (mixed-nutrient peak: 104.4±9.4 pg/ml to 114.9±15.8 pg/ml, p=NS; high-fat peak: 118.1±16.4 pg/ml to 104.4±10.8 pg/ml, p=NS). The postprandial PYY response also increased after GBP but not diet, though the increase in peak PYY did not reach statistical significance (GBP mixed-nutrient peak: 134.8±26.0 pg/ml to 220.7±52.9 pg/ml, p=0.09; GBP high-fat peak: 142.1±34.6 pg/ml to 197.9±12.7 pg/ml, p=0.07; diet mixed-nutrient peak: 99.8±8.0 pg/ml to 101.1±13.3 pg/ml, p=NS; diet high-fat peak: 105.0±8.8 pg/ml to 103.1±11.8 pg/ml, p=NS). The postprandial GLP-1 response was not affected by the macronutrient content of the meal. However, following GBP the mixed-nutrient PYY AUC0–120 was significantly greater than the high-fat PYY AUC0–120 (22081±5662 pg/ml•min versus 18711±1811 pg/ml•min, p=0.04). Conclusions Following GBP there is an increase in the postprandial stimulation of PYY and GLP-1 that is independent from caloric restriction. The phenomenon of ‘bariatric surgery-induced anorexia’ may be linked to the increased levels after GBP.

Metabolic surgery: Action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature

“…The GLP-1 analogues exenatide and liraglutide are used in the treatment of type 2 diabetes. Six studies have shown that GLP-1 is not increased after medical weight loss and may be decreased (54, 55, 71, 87–90). Only 1 of 10 studies in AGB showed an increase in GLP-1, and in that one study it was increased less than RYGB (30); the others showed no change (8, 21, 22, 56, 57, 68, 91–93).…”

“…Every malabsorptive procedure exhibits an increase in GLP-1 (for a discussion of the impact of bile acids on GLP-1, see the section below). RYGB has been especially well-studied with 19 of 20 studies showing an increase in GLP-1 after RYGB (8, 21, 37–39, 42, 49, 50, 56, 57, 68, 71, 84, 87, 90, 91, 94–96), and only 1 study showing a decrease (92). The increase in GLP-1 has been shown to occur prior to weight loss, and may contribute to the early remission of diabetes (84).…”

“…It also may inhibit appetite through secondary effects of reduced GI motility. Studies have shown that PYY either decreases (58) or does not change after medical weight loss (52, 53, 55, 87). Both AGB and SG show a general trend towards increased PYY, with 18 studies reporting a range of decreased (44), unchanged (8, 41, 42, 56, 57), and increased (21, 28, 37–40, 49, 50, 92, 97, 114, 115) PYY after intervention.…”

“…Both AGB and SG show a general trend towards increased PYY, with 18 studies reporting a range of decreased (44), unchanged (8, 41, 42, 56, 57), and increased (21, 28, 37–40, 49, 50, 92, 97, 114, 115) PYY after intervention. Interestingly, the malabsorptive procedures show a uniform increase in PYY (8, 21, 30, 37–39, 42, 44, 49, 56, 57, 87, 92, 96, 116). The mechanism of how PYY is increased is unclear, but may be related to early contact with nutrients or altered bile flow; bile acid sequestration shows mixed effects for PYY (decreased (117), no change (104), increased in rats (101)).…”

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“…The main actors in metabolic control and the reversion of complications could be the elevated concentrations of GIP, GLP-1 and PYY, resulting from an early contact between the L cell and raw nutrients [48][49][50] as well as the interaction between biliary salts and pancreatic juices, all which are promoted by procedures such as biliary pancreatic derivation, gastric bypass [51], duodenojejunal bypass [52] and adaptive enterectomy. Although it was considered a mixed procedure (restrictive and malabsorptive), in gastric bypass the malabsoptive component seems to contribute to only 11% of the overall decrease in energetic absorption [53], suggesting that it holds its main activity as a metabolic procedure.…”