自从120年前约瑟夫·巴宾斯基和阿尔弗雷德·弗洛利希首次描述下丘脑肥胖(HyOb)以来,分子遗传实验室技术的进步使我们能够阐明控制食欲和体重调节连接下丘脑的复杂神经回路的各种组成部分,脑垂体,脑干,脂肪组织,胰腺和胃肠道。在人口级常见肥胖患病率不断增加的背景下,先天性幸存者的数量(例如,隔光学发育不良,Prader-Willi综合征)和获得性(例如中枢神经系统肿瘤)下丘脑疾病正在增加,由于早期的诊断和管理以及更好的肿瘤治疗。尽管到目前为止,几种食欲调节肽的发现已经导致了一系列针对单基因肥胖综合征的靶向分子疗法的发展,除了这些疾病之外,这些发现还没有转化为其他形式的HyOb的有效治疗方法的发展。这篇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理解。并探讨我们目前对HyOb病理生理学的认识。
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.