Peptide Tyrosine-Tyrosine Triggers GLP-2-Mediated Intestinal Hypertrophy After Roux-en-Y Gastric Bypass.

PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB. We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery. RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls. The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.

Pérez-Arana GM ，Díaz-Gómez A ，Camacho-Ramírez A ，Ribelles-García A ，Almorza-Gomar D ，Gracia-Romero M ，Prada-Oliveira JA ... -  《-》

Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery.

Svane MS ，Jørgensen NB ，Bojsen-Møller KN ，Dirksen C ，Nielsen S ，Kristiansen VB ，Toräng S ，Wewer Albrechtsen NJ ，Rehfeld JF ，Hartmann B ，Madsbad S ，Holst JJ ... -  《-》

Similar Gut Hormone Secretions Two Years After One Anastomosis Gastric Bypass and Roux-en-Y Gastric Bypass: a Pilot Study.

One-anastomosis gastric bypass (OAGB) is as effective as Roux-en-Y gastric bypass (RYGB) regarding weight loss and diabetes remission. However, there are no data on gut hormone secretions after OAGB. The aim of this study was to compare fasting and postprandial secretions of gut and pancreatic hormones in OAGB versus RYGB patients. Twenty-nine patients, 16 OAGB- and 13 RYGB-operated, underwent a liquid mixed-meal tolerance test at 2 years' post-surgery. Blood was sampled before and 15, 30, 60, 90, and 120 min after meal for plasma measurement of glucose, C-peptide, insulin, glucagon, GLP-1, GIP, GLP-2, PYY, and ghrelin. Percentage of total weight loss 2 years post-surgery were -33.9 ± 1.8% for OAGB and -31.2 ± 1.6% for RYGB (p = 0.6). Four patients with persistent diabetes were excluded for further analysis. Fasting and postprandial glucose levels (peaks and area under curve values) were similar between groups. HOMA index was lower in the OAGB group (0.8 ± 0.1 vs 1.3 ± 0.2 in RYGB, p < 0.05). Levels of C-peptide (or insulin) measured at 30 min were significantly lower in OAGB vs RYGB patients (6.9 ± 0.5 vs 9.7 ± 1.1 µg/l, p < 0.05). No difference was observed between OAGB and RYGB groups for GLP-1, GLP-2, PYY, or ghrelin postprandial secretions, but GIP tended to be lower in OAGB vs RYGB patients (756 ± 155 vs 1100 ± 188 pg/ml for postprandial peak concentrations, p = 0.06). This is the first clinical study showing that OAGB procedure, like RYGB, results in high postprandial secretions of gut hormones, in particular GLP-1. Clinical Trials NCT03482895.

De Bandt D ，Rives-Lange C ，Frigout Y ，Bergerot D ，Blanchard A ，Le Gall M ，Lacorte JM ，Chevallier JM ，Czernichow S ，Poghosyan T ，Carette C ，Le Beyec J ... -  《-》

GLP-1 and PYY(3-36) reduce high-fat food preference additively after Roux-en-Y gastric bypass in diet-induced obese rats.

Roux-en-Y gastric bypass (RYGB) modifies various aspects of eating behavior in morbidly obese individuals to cause marked and lasting weight loss and improvements in metabolic health, but the underlying mechanisms remain poorly understood. To assess the relative contributions of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY3-36), whose circulating levels are enhanced by RYGB, in the reduced high-fat (HF) food preference that develops postoperatively. University hospital, Würzburg, Germany. HF diet-induced obese male Wistar rats underwent RYGB (n = 11) or sham (n = 7) surgeries and were subsequently maintained on a choice of low-fat (10% calories from fat) and HF (60% calories from fat) diets. From postoperative weeks 4 to 6, acute feeding studies were performed in which the selective GLP-1 receptor antagonist exendin-9 (30 μg/kg), the second-generation selective Y2 receptor antagonist JNJ-31020028 (10 mg/kg), or a combination of both drugs was administered intraperitoneally. During the observational period weight, adiposity and total food intake were lower while postprandial plasma GLP-1 and peptide tyrosine tyrosine levels were higher for RYGB-operated compared with sham-operated rats. There was a gradual shift in preference from HF to low-fat food in RYGB-operated rats by postoperative week 3. Single antagonist treatments had a relatively modest impact on HF food preference in rats from both surgical groups. However, dual antagonist treatment caused a striking increase in HF food preference specifically in RYGB-operated rats. GLP-1 and peptide tyrosine tyrosine 3-36 reduce HF food preference additively after RYGB supporting the use of gut hormone combination strategies for healthier feeding behavior.

Dischinger U ，Corteville C ，Otto C ，Fassnacht M ，Seyfried F ，Hankir MK ... -  《-》

The Leading Role of Peptide Tyrosine Tyrosine in Glycemic Control After Roux-en-Y Gastric Bypass in Rats.

Camacho-Ramírez A ，Prada-Oliveira JA ，Ribelles-García A ，Almorza-Gomar D ，Pérez-Arana GM ... -  《-》