Obesity treatment effect in danish children and adolescents carrying melanocortin-4 receptor mutations

Trier C,Andersson Ea,Quan S,Gamborg M,Pedersen O,Schnurr Tm,Frithioff-Bojsoe C,Svendstrup M,Hollensted M,Bille Ds,Holm Jc,Fonvig Ce,Hansen T,Balslev-Harder M,Lund Mav,Gjesing Ap,Rui G,Nielsen Trh,Angquist L

doi:10.1530/ey.18.11.5

Abstract

This study investigated the influence of MC4R variants on treatment effectiveness in a large cohort undergoing an outpatient treatment program. Carriers of MC4R loss-of-function (LoF) variants showed a lack of improvement in BMI, in contrast to non LoF carriers.

Highlights

The Melanocortin-4 Receptor (MC4R) is expressed throughout the brain, especially in the hypothalamus, and the encodedHospital, Kolding, Denmark 8 BGI-Shenzhen, Shenzhen, China 9 Ferring Pharmaceuticals, Copenhagen, Denmark 10 The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark protein regulates appetite and energy expenditure [1]
Objectives To determine the prevalence of Melanocortin-4 Receptor (MC4R) mutations in a cohort of children and adolescents with overweight or obesity and to determine whether treatment responses differed between carriers and noncarriers
When comparing phenotypic changes after lifestyle intervention between groups A and B, we found a significant difference in body mass index (BMI) standard deviation score (SDS): groups A and Ba (group B) decreased their BMI SDS, while group A did not (p = 0.005)

Summary

Introduction

The Melanocortin-4 Receptor (MC4R) is expressed throughout the brain, especially in the hypothalamus, and the encodedHospital, Kolding, Denmark 8 BGI-Shenzhen, Shenzhen, China 9 Ferring Pharmaceuticals, Copenhagen, Denmark 10 The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark protein regulates appetite and energy expenditure [1]. While the prevalence of carriers of MC4R mutations varies with ethnicity [5,6,7], up to 2% carry damaging mutations in MC4R among samples of non-consanguineous individuals with obesity of European descent, making MC4R deficiency the most common form of monogenic obesity [4]. Based on studies including children with damaging MC4R mutations, specific characteristics have been associated with MC4R deficiency, namely increased fat and lean mass, increased linear growth, increased bone mineral density, hyperphagia, and hyperinsulinemia [8, 9]. The above phenotype characteristics of carriers of damaging MC4R mutations remain controversial as other studies have failed to replicate them [11,12,13,14,15]

Objectives

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Results

Conclusion