Myogenic oxidative imbalance interferes with antral motility in obese subjects

Annunziata Scirocco, Lucia Pallotta, Marco Rengo, Antonia Ignazzi, Marilia Carabotti, Alessia Cicenia, Rosa Vona, Piero Chirletti, Maria Antonietta Maselli, Rossella Donghia, Mariagrazia Coluzzi, Paola Matarrese, Gianfranco Silecchia, Carola Severi

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)820-827
Number of pages8
JournalDigestive and Liver Disease
Volume50
Issue number8
DOIs
Publication statusPublished - Aug 2018

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Keywords

  • Acetophenones/pharmacology
  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Relaxation/drug effects
  • Muscle, Smooth/physiopathology
  • NLR Family, Pyrin Domain-Containing 3 Protein/genetics
  • Nitric Oxide Synthase Type III/metabolism
  • Obesity, Morbid/pathology
  • Oxidative Stress/drug effects
  • Pyloric Antrum/drug effects
  • Signal Transduction/drug effects
  • Vasoactive Intestinal Peptide/pharmacology
  • Young Adult

Cite this

Scirocco, A., Pallotta, L., Rengo, M., Ignazzi, A., Carabotti, M., Cicenia, A., Vona, R., Chirletti, P., Maselli, M. A., Donghia, R., Coluzzi, M., Matarrese, P., Silecchia, G., & Severi, C. (2018). Myogenic oxidative imbalance interferes with antral motility in obese subjects. Digestive and Liver Disease, 50(8), 820-827. https://doi.org/10.1016/j.dld.2018.03.005