Abstract：
Lipodystrophy syndromes are rare diseases of genetic or acquired origin, characterized by quantitative and qualitative defects in adipose tissue. The metabolic consequences of lipodystrophy syndromes, such as insulin resistant diabetes, hypertriglyceridemia and hepatic steatosis, are frequently very difficult to treat, resulting in significant risks of acute and/or chronic complications and of decreased quality of life. The production of leptin by lipodystrophic adipose tissue is decreased, more severely in generalized forms of lipodystrophy, where adipose tissue is absent from almost all body fat depots, than in partial forms of the disease, where lipoatrophy affects only some parts of the body and can be associated with increased body fat in other anatomical regions. Several lines of evidence in preclinical and clinical models have shown that leptin replacement therapy could improve the metabolic complications of lipodystrophy syndromes. Metreleptin, a recombinant leptin analogue, was approved as an orphan drug to treat the metabolic complications of leptin deficiency in patients with generalized lipodystrophy in the USA or with either generalized or partial lipodystrophy in Japan and Europe. In this brief review, we will discuss the benefits and limitations of this therapy, and the new expectations arising from the recent development of a therapeutic monoclonal antibody able to activate the leptin receptor.
摘要：
脂肪营养不良综合征是罕见的遗传或获得性疾病，以脂肪组织的定量和定性缺陷为特征。脂肪营养不良综合征的代谢后果，比如胰岛素抵抗型糖尿病，高甘油三酯血症和肝性脂肪变性，通常很难治疗，导致急性和/或慢性并发症和生活质量下降的重大风险。由脂肪营养不良的脂肪组织产生的瘦素减少，在全身性脂肪营养不良中更严重，几乎所有身体脂肪库都没有脂肪组织，而不是部分形式的疾病，其中脂肪萎缩仅影响身体的某些部位，并且可能与其他解剖区域的体内脂肪增加有关。临床前和临床模型中的一些证据表明，瘦素替代疗法可以改善脂肪营养不良综合征的代谢并发症。Metreleptin,一种重组瘦素类似物,在美国被批准为孤儿药，用于治疗全身性脂肪营养不良或日本和欧洲全身性或部分脂肪营养不良患者的瘦素缺乏的代谢并发症。在这个简短的审查，我们将讨论这种疗法的益处和局限性，以及最近开发能够激活瘦素受体的治疗性单克隆抗体带来的新期望。
