Department of Physiology, University of Santiago de Compostela, Spain.
Obes Facts. 2009;2(2):126-35. doi: 10.1159/000209251. Epub 2009 Apr 3.
The hypothalamus is a specialised area in the brain that integrates the control of energy homeostasis, regulating both food intake and energy expenditure. The classical theory for hypothalamic feeding control is mainly based on the relationship between peripheral signals and neurotransmitters/neuromodulators in the central nervous system. Thus, hypothalamic neurons respond to peripheral signals, such as hormones and nutrients, by modifying the synthesis of neuropeptides. Despite the well-established role of these hypothalamic networks, increasing evidence indicates that the modulation of lipid metabolism in the hypothalamus plays a critical role in feeding control. In fact, the pharmacologic and genetic targeting of key enzymes from these pathways, such as AMP-activated protein kinase, acetyl-CoA carboxylase, carnitine palmitoyltransferase 1, fatty acid synthase, and malonyl-CoA decarboxylase, has a profound effect on food intake and body weight. Here, we review what is currently known about the relationship between hypothalamic lipid metabolism and whole body energy homeostasis. Defining these novel mechanisms may offer new therapeutic targets for the treatment of obesity and its associated pathologies.
下丘脑是大脑中一个专门的区域，它整合了能量平衡的控制，调节食物摄入和能量消耗。经典的下丘脑进食控制理论主要基于外周信号与中枢神经系统中神经递质/神经调质之间的关系。因此，下丘脑神经元通过改变神经肽的合成对外周信号（如激素和营养物质）做出反应。尽管这些下丘脑网络的作用已经得到充分证实，但越来越多的证据表明，下丘脑脂质代谢的调节在进食控制中起着关键作用。事实上，这些途径中的关键酶，如 AMP 激活蛋白激酶、乙酰辅酶 A 羧化酶、肉碱棕榈酰基转移酶 1、脂肪酸合酶和丙二酰辅酶 A 脱羧酶的药理学和遗传学靶向，对食物摄入和体重有深远的影响。在这里，我们回顾了目前已知的下丘脑脂质代谢与全身能量平衡之间的关系。定义这些新的机制可能为肥胖及其相关病理的治疗提供新的治疗靶点。
