Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin. An in-depth understanding of the pathogenesis, clinical presentation, and therapeutic targets of hypothalamic obesity relies on the comprehension of the physiological basis of hypothalamic pathways governing bodyweight control, the mechanisms (either genetic or acquired) whereby they are perturbed, and the consequences of such perturbation. In this Review, we provide a synoptic overview of hypothalamic obesity, from basic mechanisms to clinical perspectives, with a major focus on current developments and new avenues for the diagnosis and precise treatment of these rare forms of obesity.

中文翻译：

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下丘脑性肥胖：从基本机制到临床观点


尽管肥胖的性质多种多样，但有令人信服的遗传、临床和实验证据支持大脑回路对这种情况的重要贡献。下丘脑包含体重稳态的主要调节回路，其失调会导致肥胖。尽管下丘脑通路的功能扰动可能是常见肥胖形式的基础，但下丘脑肥胖一词已被创建来定义那些罕见的严重肥胖形式，其中可以识别出明确的下丘脑底物，无论是遗传性的还是获得性的。深入了解下丘脑性肥胖的发病机制、临床表现和治疗靶点取决于对控制体重控制的下丘脑通路的生理基础、它们受到干扰的机制（遗传或获得性）以及这种扰动的后果的理解。在这篇综述中，我们提供了下丘脑肥胖的概要概述，从基本机制到临床观点，主要关注这些罕见肥胖的当前发展和诊断和精确治疗的新途径。