Farooqi I Sadaf, O'Rahilly Stephen
MRC Metabolic Diseases UnitMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
MRC Metabolic Diseases UnitMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
J Endocrinol. 2014 Oct;223(1):T63-70. doi: 10.1530/JOE-14-0480.
The discovery of leptin has provided a robust framework upon which our current understanding of the mechanisms involved in energy homeostasis has been built. In this review, we describe how the identification of humans with mutations in the genes encoding leptin and the leptin receptor and the characterisation of the associated clinical phenotypes have provided insights into the role of leptin-responsive pathways in the regulation of eating behaviour, intermediary metabolism and the onset of puberty. Importantly, administration of recombinant human leptin in leptin deficiency represents the first mechanistically based targeted therapy for obesity and has provided immense clinical benefits for the patients concerned. In subsequent years, we and others have shown that human obesity can result from a multiplicity of defects in the pathways downstream of leptin signalling within the brain.
瘦素的发现为我们目前对能量稳态相关机制的理解构建了一个坚实的框架。在本综述中，我们描述了携带瘦素和瘦素受体编码基因突变的人类的鉴定以及相关临床表型的特征，如何为瘦素反应途径在饮食行为、中间代谢和青春期启动调节中的作用提供了见解。重要的是，在瘦素缺乏症中给予重组人瘦素代表了第一种基于机制的肥胖靶向治疗方法，并为相关患者带来了巨大的临床益处。在随后的几年里，我们和其他人已经表明，人类肥胖可能源于大脑中瘦素信号下游途径的多种缺陷。
