Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Front Neuroendocrinol. 2010 Jul;31(3):377-93. doi: 10.1016/j.yfrne.2010.06.002. Epub 2010 Jun 17.
Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent "proof of concept" clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.
瘦素调节能量平衡和生殖、神经内分泌、免疫和代谢功能。在这篇综述中，我们描述了瘦素在人体生理学中的作用，并回顾了最近使用重组人瘦素治疗先天性瘦素缺乏症、与能量不足状态相关的低瘦素血症和与普通肥胖相关的高瘦素血症的“概念验证”临床试验的证据。由于大多数肥胖者对瘦素的耐受性或抵抗性很大，因此瘦素的治疗用途目前仅限于完全或部分瘦素缺乏的患者，包括下丘脑性闭经和脂肪萎缩。在这些能量不足的状态下给予瘦素可能有助于恢复相关的神经内分泌、代谢和免疫功能以及骨代谢。目前，瘦素治疗可用于先天性瘦素缺乏症和先天性脂肪萎缩症患者。瘦素治疗下丘脑性闭经和获得性脂肪萎缩的长期疗效和安全性正在研究中。瘦素与潜在的瘦素敏化剂联合治疗是否对治疗普通肥胖有效，以及瘦素是否在减肥维持中发挥作用，人们对此寄予厚望。
