Oxytocin receptor signaling contributes to the mitochondrial integrity and maintain gastric mucosal homeostasis in male mice.

The role of oxytocin receptor (OXTR) signaling in the stomach remains poorly understood. This study investigates the physiological and pathophysiological role of OXTR signaling in parietal cells. Using wild type (wt), OXT null and OXTR null mice fed either a standard diet (SD) or a high fat diet (HFD), we examined the effects of OXT and OXTR signaling on gastric mucosa histology and function. SD-fed mice lacking active OXTR/OXT showed mucosal hyperplasia, which was reversed by subcutaneous OXT administration in OXT null mice. HFD-fed wt mice developed typical gastric mucosal hyperplasia, parietal cell atrophy with mitochondrial damage, and impaired 18F-fluorodeoxyglucose uptake. Subcutaneous OXT administration ameliorated these effects in HFD-fed wt mice, but not in OXTR null mice, suggesting that OXTR activation likely preserves mitochondrial integrity. Our findings support the hypothesis that OXTR signaling in parietal cells is essential for maintaining gastric mucosal metabolic homeostasis and protects against diet-induced gastric pathology.