TY - JOUR
T1 - Myogenic oxidative imbalance interferes with antral motility in obese subjects
AU - Scirocco, Annunziata
AU - Pallotta, Lucia
AU - Rengo, Marco
AU - Ignazzi, Antonia
AU - Carabotti, Marilia
AU - Cicenia, Alessia
AU - Vona, Rosa
AU - Chirletti, Piero
AU - Maselli, Maria Antonietta
AU - Donghia, Rossella
AU - Coluzzi, Mariagrazia
AU - Matarrese, Paola
AU - Silecchia, Gianfranco
AU - Severi, Carola
N1 - Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - BACKGROUND: 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.AIM: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo.METHODS: 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.RESULTS: 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.CONCLUSION: Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress.
AB - BACKGROUND: 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.AIM: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo.METHODS: 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.RESULTS: 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.CONCLUSION: Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress.
KW - Acetophenones/pharmacology
KW - Adult
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Muscle Relaxation/drug effects
KW - Muscle, Smooth/physiopathology
KW - NLR Family, Pyrin Domain-Containing 3 Protein/genetics
KW - Nitric Oxide Synthase Type III/metabolism
KW - Obesity, Morbid/pathology
KW - Oxidative Stress/drug effects
KW - Pyloric Antrum/drug effects
KW - Signal Transduction/drug effects
KW - Vasoactive Intestinal Peptide/pharmacology
KW - Young Adult
U2 - 10.1016/j.dld.2018.03.005
DO - 10.1016/j.dld.2018.03.005
M3 - Article
VL - 50
SP - 820
EP - 827
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
SN - 1590-8658
IS - 8
ER -