Abstract

The central nervous system (CNS) receives information from afferent neurons, circulating hormones and absorbed nutrients and integrates this information to orchestrate the actions of the neuroendocrine and autonomic nervous systems in maintaining systemic metabolic homeostasis. Particularly the arcuate nucleus of the hypothalamus (ARC) is of pivotal importance for primary sensing of adiposity signals, such as leptin and insulin, and circulating nutrients, such as glucose. Importantly, energy state-sensing neurons in the ARC not only regulate feeding but at the same time control multiple physiological functions, such as glucose homeostasis, blood pressure and innate immune responses. These findings have defined them as master regulators, which adapt integrative physiology to the energy state of the organism. The disruption of this fine-tuned control leads to an imbalance between energy intake and expenditure as well as deregulation of peripheral metabolism. Improving our understanding of the cellular, molecular and functional basis of this regulatory principle in the CNS could set the stage for developing novel therapeutic strategies for the treatment of obesity and metabolic syndrome. In this review, we summarize novel insights with a particular emphasis on ARC neurocircuitries regulating food intake and glucose homeostasis and sensing factors that inform the brain of the organismal energy status.

中文翻译：

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代谢的弓形核依赖性调节 - 肥胖和糖尿病的途径

摘要

中枢神经系统 (CNS) 接收来自传入神经元、循环激素和吸收的营养物质的信息，并整合这些信息以协调神经内分泌和自主神经系统在维持全身代谢稳态中的作用。特别是下丘脑弓状核 (ARC) 对于肥胖信号（如瘦素和胰岛素）和循环营养物质（如葡萄糖）的初级感知至关重要。重要的是，ARC 中的能量状态感应神经元不仅可以调节进食，还可以控制多种生理功能，例如葡萄糖稳态、血压和先天免疫反应。这些发现将它们定义为主要调节器，使综合生理学适应有机体的能量状态。这种微调控制的破坏导致能量摄入和消耗之间的不平衡以及外周代谢的失调。提高我们对中枢神经系统这一调节原理的细胞、分子和功能基础的理解，可以为开发治疗肥胖和代谢综合征的新治疗策略奠定基础。在这篇综述中，我们总结了新的见解，特别强调了调节食物摄入和葡萄糖稳态的 ARC 神经电路以及通知大脑有机体能量状态的传感因素。这种中枢神经系统调节原理的分子和功能基础可以为开发治疗肥胖和代谢综合征的新治疗策略奠定基础。在这篇综述中，我们总结了新的见解，特别强调了调节食物摄入和葡萄糖稳态的 ARC 神经电路以及通知大脑有机体能量状态的传感因素。这种中枢神经系统调节原理的分子和功能基础可以为开发治疗肥胖和代谢综合征的新治疗策略奠定基础。在这篇综述中，我们总结了新的见解，特别强调了调节食物摄入和葡萄糖稳态的 ARC 神经电路以及通知大脑有机体能量状态的传感因素。