van Swieten M M H, Pandit R, Adan R A H, van der Plasse G
Department of Translational Neuroscience, Division of Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Master's Program Neuroscience and Cognition, Utrecht University, The Netherlands.
Department of Translational Neuroscience, Division of Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
J Chem Neuroanat. 2014 Nov;61-62:207-20. doi: 10.1016/j.jchemneu.2014.05.004. Epub 2014 Jul 4.
The anorexigenic hormone leptin plays an important role in the control of food intake and feeding-related behavior, for an important part through its action in the hypothalamus. The adipose-derived hormone modulates a complex network of several intercommunicating orexigenic and anorexigenic neuropeptides in the hypothalamus to reduce food intake and increase energy expenditure. In this review we present an updated overview of the functional role of leptin in respect to feeding and feeding-related behavior per distinct hypothalamic nuclei. In addition to the arcuate nucleus, which is a major leptin sensitive hub, leptin-responsive neurons in other hypothalamic nuclei, including the, dorsomedial-, ventromedial- and paraventricular nucleus and the lateral hypothalamic area, are direct targets of leptin. However, leptin also modulates hypothalamic neurons in an indirect manner, such as via the melanocortin system. The dissection of the complexity of leptin's action on the networks involved in energy balance is subject of recent and future studies. A full understanding of the role of hypothalamic leptin in the regulation of energy balance requires cell-specific manipulation using of conditional deletion and expression of leptin receptors. In addition, optogenetic and pharmacogenetic tools in combination with other pharmacological (such as the recent discovery of a leptin receptor antagonist) and neuronal tracing techniques to map the circuit, will be helpful to understand the role of leptin receptor expressing neurons. Better understanding of these circuits and the involvement of leptin could provide potential sites for therapeutic interventions in obesity and metabolic diseases characterized by dysregulation of energy balance.
厌食激素瘦素在控制食物摄入和与进食相关的行为中起着重要作用，其中很大一部分是通过其在下丘脑的作用实现的。这种源自脂肪组织的激素调节下丘脑内几个相互连通的促食欲和厌食神经肽的复杂网络，以减少食物摄入并增加能量消耗。在这篇综述中，我们针对每个不同的下丘脑核团，对瘦素在进食及与进食相关行为方面的功能作用进行了更新概述。除了作为主要瘦素敏感枢纽的弓状核外，其他下丘脑核团中的瘦素反应性神经元，包括背内侧核、腹内侧核、室旁核和下丘脑外侧区，都是瘦素的直接作用靶点。然而，瘦素也以间接方式调节下丘脑神经元，例如通过黑皮质素系统。剖析瘦素对能量平衡相关网络作用的复杂性是近期和未来研究的主题。要全面了解下丘脑瘦素在能量平衡调节中的作用，需要使用条件性缺失和瘦素受体表达等细胞特异性操作方法。此外，光遗传学和药物遗传学工具与其他药理学方法（如最近发现的瘦素受体拮抗剂）以及用于绘制神经回路的神经元追踪技术相结合，将有助于理解表达瘦素受体的神经元的作用。更好地理解这些神经回路以及瘦素的参与情况，可能为肥胖症和以能量平衡失调为特征的代谢性疾病提供潜在的治疗干预靶点。
