Hospital for Children and Adolescents, University of Leipzig, Germany.
J Investig Med. 2009 Oct;57(7):784-8. doi: 10.2310/JIM.0b013e3181b9163d.
The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and energy expenditure leading to a morbidly obese phenotype and a disrupted regulation in neuroendocrine and immune function and in glucose and fat metabolism. Observational and interventional studies in humans with (complete) congenital leptin deficiency caused by mutations in the leptin gene or with relative leptin deficiency as seen in states of negative energy balance such as lipoatrophy, anorexia nervosa, or exercise-induced hypothalamic and neuroendocrine dysfunction have contributed to the elucidation of the pathophysiological role of leptin in these conditions and of the clinical significance of leptin administration in these subjects. More specifically, interventional studies have demonstrated that several neuroendocrine, metabolic, or immune disturbances in these states could be restored by leptin administration. Leptin replacement therapy is currently available through a compassionate use program for congenital complete leptin deficiency and under an expanded access program to subjects with leptin deficiency associated with congenital or acquired lipoatrophy. In addition, leptin remains a potentially forthcoming treatment for several other states of energy deprivation including anorexia nervosa or milder forms of hypothalamic amenorrhea pending appropriate clinical trials.
瘦素的发现极大地促进了我们对脂肪组织代谢重要性的理解，并且表明瘦素缺乏和瘦素过多都与严重的代谢、内分泌和免疫后果有关。我们和其他人已经表明，瘦素在人类中的一个主要作用是介导对能量剥夺的神经内分泌适应。由于瘦素和瘦素受体基因的基因突变，人类出现了不受调节的食物摄入和能量消耗，导致病态肥胖表型以及神经内分泌和免疫功能以及葡萄糖和脂肪代谢的紊乱调节。通过对由于瘦素基因突变导致的（完全）先天性瘦素缺乏症或由于能量负平衡状态（如脂肪萎缩、神经性厌食症或运动引起的下丘脑和神经内分泌功能障碍）导致的相对瘦素缺乏症的人类进行观察性和干预性研究，有助于阐明瘦素在这些疾病中的病理生理作用以及瘦素在这些患者中的临床意义。更具体地说，干预性研究表明，这些状态中的几种神经内分泌、代谢或免疫紊乱可以通过瘦素给药来恢复。瘦素替代疗法目前可通过对先天性完全瘦素缺乏症的同情使用计划获得，并可通过扩大获取途径获得与先天性或获得性脂肪萎缩相关的瘦素缺乏症患者。此外，在进行适当的临床试验之前，瘦素仍然是治疗包括神经性厌食症或更温和的下丘脑性闭经在内的其他几种能量剥夺状态的潜在治疗方法。
