Asker Mohammed, Krieger Jean-Philippe, Maric Ivana, Bedel Emre, Steen Jenny, Börchers Stina, Wen Yuxiang, Longo Francesco, Aronsson Patrik, Winder Michael, Doyle Robert P, Hayes Matthew R, Skibicka Karolina P
Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden.
JCI Insight. 2025 May 22;10(10). doi: 10.1172/jci.insight.190108.
Oxytocin plays a key role in reproductive physiology but has recently garnered interest for its involvement in modulating feeding behavior. The vagus nerve contributes to feeding behavior control, as well as other gastrointestinal functions. Oxytocin receptors (OTR) are expressed on the vagus, but their role is poorly understood. Herein, we evaluated the contribution of the vagal OTR to food intake and body weight control in male and female rats. Virogenetic knockdown of vagal OTR resulted in reduced body weight and food intake in male rats. Loss of OTR in the vagus also resulted in suppressed locomotor activity in males but hyperactivity in females. Importantly, rats with vagal OTR knockdown, but not controls, exhibited a significantly elevated mortality rate starting 4 weeks after knockdown, with males being disproportionately affected. Mortality followed large eating bouts and was accompanied by abnormal presence of food in the mouth and esophagus, suggesting death by aspiration or food in the airways and suggesting a crucial role of vagal OTR in upper gastrointestinal tract motility. Furthermore, in vivo experiments revealed impaired esophageal transit. Ex vivo findings indicated oxytocin's contribution to lower esophageal sphincter contraction. Our findings demonstrated a critical role for the oxytocin system: essential function of vagal OTR for esophageal transit and swallowing.
催产素在生殖生理学中发挥着关键作用,但最近因其参与调节摄食行为而受到关注。迷走神经有助于控制摄食行为以及其他胃肠功能。催产素受体(OTR)在迷走神经上表达,但其作用尚不清楚。在此,我们评估了迷走神经OTR对雄性和雌性大鼠食物摄入和体重控制的作用。迷走神经OTR的病毒介导基因敲低导致雄性大鼠体重和食物摄入量减少。迷走神经中OTR的缺失也导致雄性大鼠运动活动受抑制,但雌性大鼠出现多动。重要的是,迷走神经OTR基因敲低的大鼠(而非对照大鼠)在基因敲低4周后死亡率显著升高,雄性大鼠受影响尤为严重。死亡发生在大量进食之后,且伴有口腔和食管中异常存在食物的情况,提示因误吸或气道中有食物而死亡,这表明迷走神经OTR在上消化道运动中起关键作用。此外,体内实验显示食管转运受损。体外研究结果表明催产素对食管下括约肌收缩有作用。我们的研究结果证明了催产素系统的关键作用:迷走神经OTR对食管转运和吞咽的重要功能。