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.

Keywords: Human gastric smooth muscle cells; Obesity; Oxidative stress; Vasoactive intestinal peptide.