Sorbonne Université, INSERM, NutriOmics team, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
Institute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Nat Med. 2018 May;24(5):551-555. doi: 10.1038/s41591-018-0015-9. Epub 2018 May 7.
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.
MC4R 信号通路的遗传缺陷导致严重肥胖。三位严重肥胖的 LEPR 缺陷个体接受了 MC4R 激动剂 setmelanotide 的治疗，在 45-61 周的观察期内，摄食量和体重显著且持久减少。与以前开发和测试的 MC4R 激动剂相比，setmelanotide 具有独特的激活 T 细胞激活核因子（NFAT）信号的能力，并恢复选定 MC4R 变体的这种信号通路的功能。我们的数据证明了 setmelanotide 在治疗具有不同 MC4R 相关途径缺陷的个体中的效力。
