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

doi:10.1016/j.dld.2018.03.005

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 journal › Article

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 language	English
Pages (from-to)	820-827
Number of pages	8
Journal	Digestive and Liver Disease
Volume	50
Issue number	8
DOIs	https://doi.org/10.1016/j.dld.2018.03.005
Publication status	Published - 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

Myogenic oxidative imbalance interferes with antral motility in obese subjects. / Scirocco, Annunziata; Pallotta, Lucia; Rengo, Marco; Ignazzi, Antonia; Carabotti, Marilia; Cicenia, Alessia; Vona, Rosa; Chirletti, Piero; Maselli, Maria Antonietta; Donghia, Rossella; Coluzzi, Mariagrazia; Matarrese, Paola; Silecchia, Gianfranco; Severi, Carola.

In: Digestive and Liver Disease, Vol. 50, No. 8, 08.2018, p. 820-827.

Research output: Contribution to journal › Article

Scirocco, Annunziata ; Pallotta, Lucia ; Rengo, Marco ; Ignazzi, Antonia ; Carabotti, Marilia ; Cicenia, Alessia ; Vona, Rosa ; Chirletti, Piero ; Maselli, Maria Antonietta ; Donghia, Rossella ; Coluzzi, Mariagrazia ; Matarrese, Paola ; Silecchia, Gianfranco ; Severi, Carola. / Myogenic oxidative imbalance interferes with antral motility in obese subjects. In: Digestive and Liver Disease. 2018 ; Vol. 50, No. 8. pp. 820-827.

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title = "Myogenic oxidative imbalance interferes with antral motility in obese subjects",

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.",

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

year = "2018",

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doi = "10.1016/j.dld.2018.03.005",

language = "English",

volume = "50",

pages = "820--827",

journal = "Digestive and Liver Disease",

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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

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.

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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 -

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10.1016/j.dld.2018.03.005