Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb. This review aims to summarize our current understanding of the neuroendocrine physiology of appetite and weight regulation, and explore our current understanding of the pathophysiology of HyOb.

中文翻译：

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下丘脑肥胖中的食欲和体重调节神经内分泌回路。


自 120 多年前 Joseph Babinski 和 Alfred Fröhlich 首次描述下丘脑肥胖 (HyOb) 以来，分子遗传学实验室技术的进步使我们能够阐明连接下丘脑、垂体、脑干的控制食欲和体重调节的复杂神经回路的各个组成部分、脂肪组织、胰腺和胃肠道。在人口普遍肥胖患病率不断增加的背景下，先天性（如视神经发育不良、普瑞德-威利综合征）和后天性（如中枢神经系统肿瘤）下丘脑疾病的幸存者数量正在增加，这要归功于更早的诊断和管理以及更好的肿瘤治疗。尽管迄今为止，几种食欲调节肽的发现已导致一系列针对单基因肥胖综合征的靶向分子疗法的开发，但除了这些疾病之外，这些发现尚未转化为针对其他形式的 HyOb 的有效治疗方法的开发。本综述旨在总结我们目前对食欲和体重调节的神经内分泌生理学的认识，并探讨我们目前对 HyOb 病理生理学的认识。