vasoactive-intestinal-peptide and Obesity--Morbid

Obesity is characterized by a systemic low-grade chronic inflammatory oxidative condition that affects vascular and cardiac smooth muscle relaxation. In human antrum, relaxation is mediated by vasoactive intestinal peptide (VIP) through cAMP and cGMP signaling pathways. A genome-wide association study has demonstrated an association between VIP and obesity.. To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo.. Antral muscle strips and cells were isolated from surgical gastric samples from obese and normal weight subjects. Muscle contraction and relaxation, myogenic oxidative stress and inflammatory status were analyzed in vitro. Distal antral motility was evaluated in vivo by magnetic resonance imaging.. Obese antral muscle cells showed an oxidative-inflammatory imbalance with overexpression of NLRP3 inflammasome, increased IL-1β secretion and caspase1-activation, and reduced antioxidant capacity associated with a myogenic motor impairment of VIP-induced relaxation. The intracellular alterations were characterized by a decreased activation of the cAMP-signaling pathway and a decreased expression of eNOS. These in vitro alterations coincided with the hindering of antral motor activity observed in vivo. Apocynin treatment, counteracting oxidative stress, reverted alterations observed in obese antral muscle.. Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress.

Topics: Acetophenones; Adult; Female; Humans; Male; Middle Aged; Muscle Relaxation; Muscle, Smooth; Nitric Oxide Synthase Type III; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity, Morbid; Oxidative Stress; Pyloric Antrum; Signal Transduction; Vasoactive Intestinal Peptide; Young Adult

The Willmen gastric bubble has been used as an adjunct to weight loss in morbidly obese patients. 35 patients with morbid obesity were studied with routine manometry, esophageal 24-h-pH-measurement, and gastric emptying studies before and 4 weeks after bubble placement. During emptying studies blood samples were taken to measure gastrin, PP, CCK, VIP, neurotensin and insulin. No patient developed heartburn or regurgitation after bubble placement. Esophageal motility and LES function remained unchanged. There was no important pathological gastroesophageal reflux before and after gastric bubble. The gastric emptying time of solid food was unchanged by gastric bubble placement and the emptying time of liquids was accelerated up to normal. In patients with fasting gastrin levels less than 20 pg/ml at the beginning of the first test we found no differences in gastrin release before and after bubble insertion. In patients with primary high fasting values gastrin release was significantly increased. CCK, VIP, neurotensin and insulin levels were unchanged. With PP we measured significantly raised fasting levels after gastric bubble. We conclude that esophageal and LES functions are not altered by Willmen gastric bubble placement and that primary retardation of fluids is changed to normal. Bubble induced gastric tension increases fasting PP. In case of high fasting gastrin the bubble leads to an extremely high food response without any clinical signs.

Topics: Adult; Cholecystokinin; Esophagogastric Junction; Esophagus; Female; Gastric Acidity Determination; Gastric Emptying; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Male; Manometry; Middle Aged; Neurotensin; Obesity, Morbid; Pancreatic Polypeptide; Prostheses and Implants; Vasoactive Intestinal Peptide