MC4R Agonism Promotes Durable Weight Loss in Patients with Leptin Receptor Deficiency

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2018 May 9

PMID 29736023

Citations 129

Authors

Karine Clement

Heike Biebermann

I Sadaf Farooqi

Lex van der Ploeg

Barbara Wolters

Christine Poitou

Lia Puder

Fred Fiedorek

Keith Gottesdiener

Gunnar Kleinau

Nicolas Heyder

Patrick Scheerer

Ulrike Blume-Peytavi

Irina Jahnke

Shubh Sharma

Jacek Mokrosinski

Susanna Wiegand

Anne Muller

Katja Weiss

Knut Mai

Joachim Spranger

Annette Gruters

Oliver Blankenstein

Heiko Krude

Peter Kuhnen

Affiliations

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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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References

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