Woods Stephen C, Seeley Randy J, Cota Daniela
Department of Psychiatry, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio 45237, USA.
Annu Rev Nutr. 2008;28:295-311. doi: 10.1146/annurev.nutr.28.061807.155505.
To maintain normal activity, single cells must assure that their energy needs and utilization are continuously matched. Likewise, multicellular organisms must constantly coordinate energy intake and expenditure to maintain energy homeostasis. The brain, and the hypothalamus in particular, plays a critical role in integrating and coordinating several types of signals, including hormones and nutrients, to guarantee such homeostasis. Like single cells, the hypothalamus also profits from intracellular pathways known to work as fuel sensors to maintain energy balance. One such pathway is the mammalian target of rapamycin (mTOR). mTOR integrates different sensory inputs to regulate protein synthesis rates in individual cells, and it has recently been implicated in the central nervous system to regulate food intake and body weight as well. This review provides an overview of the role of hypothalamic intracellular fuel sensors in the overall control of energy balance and discusses the potential contribution of these fuel-sensing mechanisms to the metabolic dysregulation associated with obesity.
为维持正常活动，单细胞必须确保其能量需求与利用持续匹配。同样，多细胞生物必须不断协调能量摄入与消耗以维持能量平衡。大脑，尤其是下丘脑，在整合与协调多种信号（包括激素和营养物质）以确保这种平衡方面发挥着关键作用。与单细胞一样，下丘脑也受益于已知作为燃料传感器起作用以维持能量平衡的细胞内信号通路。其中一条这样的信号通路是雷帕霉素靶蛋白（mTOR）。mTOR整合不同的感官输入以调节单个细胞中的蛋白质合成速率，并且最近它在中枢神经系统中也被认为参与调节食物摄入和体重。本综述概述了下丘脑细胞内燃料传感器在能量平衡整体控制中的作用，并讨论了这些燃料传感机制对与肥胖相关的代谢失调的潜在影响。
