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Updated: Feb 10, 2026

Experimental Approach to Examine Leptin Signaling in the Carotid Bodies and its Effects on Control of Breathing
Published on: October 25, 2019
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency
Karine Clément1, Heike Biebermann2, I Sadaf Farooqi3
1Sorbonne Université, INSERM, NutriOmics team, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
Abstract:
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.
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