MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency
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DOI：
10.1038/s41591-018-0015-9
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发表时间：
2018-05-01
期刊：
影响因子：
82.9
通讯作者：
Kuehnen, Peter
中科院分区：
文献类型：
--
作者：
Clement, Karine;Biebermann, Heike;Kuehnen, Peter
黑素皮质素-4受体(MC4R)信号通路的遗传缺陷会导致严重肥胖。在45-61周的观察期内，三名严重肥胖的LEPR缺陷患者服用了MC4R激动剂setmelanotie，结果显著和持久地减少了吞噬功能和体重。与已开发和试验的MC4R激动剂相比，setmelanoide具有独特的激活活化T细胞核因子(NFAT)信号的能力，并对选定的MC4R变异体恢复该信号通路的功能。我们的数据证明了setmelanoide在治疗患有不同MC4R相关途径缺陷的个人方面的有效性。
Genetic defects underlying the melanocortin-4 receptor (MC4R) signaling pathway lead to severe obesity. Three severely obese LEPR-deficient individuals were administered the MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia and body weight over an observation period of 45-61 weeks. Compared to formerly developed and tested MC4R agonists, setmelanotide has the unique capability of activating nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling pathway for selected MC4R variants. Our data demonstrate the potency of setmelanotide in treatment of individuals with diverse MC4R-related pathway deficiencies.