de Lartigue Guillaume
The John B. Pierce Laboratory, New Haven, CT, USA.
Dept Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
J Physiol. 2016 Oct 15;594(20):5791-5815. doi: 10.1113/JP271538. Epub 2016 May 29.
This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie-rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high-fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade-induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity.
本综述强调了迷走神经在肥胖症发展中作用的证据，以及如何通过神经调节或药理学作用于迷走神经来治疗肥胖症。支配肠道的迷走神经在控制新陈代谢中起着重要作用。它在肠道和大脑之间传递有关营养物质数量和类型的外周信息。根据营养状况，迷走神经传入神经元表达两种不同的神经化学表型，可抑制或刺激食物摄入。长期摄入高热量饮食会降低迷走神经传入神经元对外周信号的敏感性及其促食欲受体和神经肽的组成性表达。迷走神经传入信号的这种破坏足以导致食欲亢进和肥胖。此外，迷走神经的神经调节可用于治疗肥胖症。尽管其机制尚不清楚，但迷走神经刺激可防止因高脂饮食导致的体重增加。在小型临床研究中，已证明迷走神经刺激对抑郁症或癫痫患者有促进体重减轻的作用。抑制迷走神经的迷走神经阻滞会导致显著体重减轻。迷走神经阻滞被认为是通过抑制肥胖中产生的异常促食欲信号来实现体重减轻的一种假定机制。本文还提出了开发未来针对迷走神经治疗肥胖症的药物疗法的方法和分子靶点。总之，有充分证据表明迷走神经参与了肥胖症的发展，并且它正被证明是治疗肥胖症的一个有吸引力的靶点。
