Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, 266021, Shandong, China.
Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, 266021, Shandong, China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):3186-3191. doi: 10.1016/j.bbrc.2018.08.120. Epub 2018 Aug 23.
Obesity has become a global problem due to its sharply increased prevalence and associated complications. Orexin and opioid signaling can regulate feeding behavior and represent potential therapeutic targets for obesity. In the present experiment, we sought to ascertain the effects of orexin-A and μ-opioid signaling regulation in the basomedial amygdala (BMA) on feeding and investigate the physiology of gastric distension (GD)-responsive neurons in a diet-induced obesity (DIO) and diet-induced obesity resistance (DR) rat model. Intra-BMA infusions of orexin-A increased the firing of BMA GD neurons and increased food intake, and that these effects could be abolished by pretreatment with the orexin-1 receptor (OX-1R) antagonist SB334867, these effects could also be somewhat attenuated by co-administration of naloxone. In the DIO and DR rats, mRNA expression of OX-1R and μ-opioid receptors were increased in the BMA. Our results strongly suggest that orexin-A and opioid signaling in the BMA play a major role in regulating GD neuronal excitability and feeding behavior in obesity.
肥胖症由于其发病率的急剧上升及其相关并发症已成为一个全球性问题。食欲素和阿片信号可以调节摄食行为，代表了肥胖症的潜在治疗靶点。在本实验中，我们旨在确定下丘脑基底部（BMA）中食欲素-A 和 μ-阿片信号调节对摄食的影响，并研究饮食诱导肥胖（DIO）和饮食诱导肥胖抵抗（DR）大鼠模型中胃扩张（GD）反应神经元的生理学。BMA 内注射食欲素-A 增加了 BMA GD 神经元的放电并增加了食物摄入，而这些作用可以被食欲素-1 受体（OX-1R）拮抗剂 SB334867 预处理所消除，纳洛酮的共同给药也可以使这些作用有所减弱。在 DIO 和 DR 大鼠中，BMA 中 OX-1R 和 μ-阿片受体的 mRNA 表达增加。我们的研究结果强烈表明，BMA 中的食欲素-A 和阿片信号在调节 GD 神经元兴奋性和肥胖症中的摄食行为方面发挥着重要作用。
