Department of Pathophysiology, School of Basic Medicine, Qingdao University, Shandong, Qingdao 266071, China.
Department of Pathophysiology, School of Basic Medicine, Qingdao University, Shandong, Qingdao 266071, China.
Neuropeptides. 2018 Jun;69:26-38. doi: 10.1016/j.npep.2018.04.001. Epub 2018 Apr 6.
Obesity is a global public health problem. Orexin and endocannabinoid signaling in the hypothalamus have been shown to regulate feeding and are promising molecular targets for obesity treatment. In this study, we attempted to analyze effects of orexin-A and endocannabinoid signaling modulation in the arcuate nucleus (Arc) on feeding and glucose-responsive (GR) neurons physiology in a diet-induced obesity (DIO) and diet-induced obesity resistant (DR) rat model. Administration of orexin-A or cannabinoid receptor type-1 (CBR) antagonist AM251 altered the firing of GR neurons in the Arc. The effects of orexin-A were eliminated by pre-administrating orexin-1 receptor (OX-1R) antagonist SB334867, respectively. Behavioral studies showed that orexin-A increased food intake, while AM251 reduced feeding. Histological studies showed that mRNA and protein expression of OX-1R (orexin-1 receptor) and CBR were increased in the Arc of DIO and DR rats. Our results strongly suggest that orexin-A and endocannabinoid signaling in Arc plays an important role in regulating GR neuronal excitability and food intake in obesity.
肥胖是一个全球性的公共健康问题。现已证明，下丘脑的食欲素和内源性大麻素信号可调节摄食，是肥胖治疗有前途的分子靶点。在这项研究中，我们试图分析下丘脑弓状核（Arc）中食欲素-A 和内源性大麻素信号调节对饮食诱导肥胖（DIO）和饮食诱导肥胖抵抗（DR）大鼠模型中摄食和葡萄糖反应（GR）神经元生理学的影响。食欲素-A 或大麻素受体 1（CBR）拮抗剂 AM251 的给药改变了 Arc 中 GR 神经元的放电。分别用食欲素-1 受体（OX-1R）拮抗剂 SB334867 预处理消除了食欲素-A 的作用。行为研究表明，食欲素-A 增加了食物摄入量，而 AM251 则减少了摄食。组织学研究表明，DIO 和 DR 大鼠 Arc 中 OX-1R（食欲素-1 受体）和 CBR 的 mRNA 和蛋白表达增加。我们的研究结果强烈表明，Arc 中的食欲素-A 和内源性大麻素信号在调节肥胖时 GR 神经元兴奋性和摄食方面起着重要作用。
