Melanocortin-4 Receptor and Lipocalin 2 Gene Variants in Spanish Children with Abdominal Obesity: Effects on BMI-SDS After a Lifestyle Intervention.

Morell-Azanza Morell-Azanza,Hebebrand Hebebrand,Ojeda-Rodríguez Ojeda-Rodríguez,Giuranna Giuranna,Azcona-Sanjulián Azcona-Sanjulián,Hinney Hinney,Marti Marti

doi:10.3390/nu11050960

Abstract

Mutations leading to a reduced function of the melanocortin-4 receptor (MC4R) exert a major gene effect on extreme obesity. Recently it was shown that the bone derived hormone lipocalin 2 (LCN2) binds to the MC4R and activates a MC4R dependent anorexigenic pathway. We identified mutations in both genes and screened the effects of MC4R and LCN2 mutations on eating behavior and weight change after a lifestyle intervention. One hundred and twelve children (11.24 ± 2.6 years, BMI-SDS 2.91 ± 1.07) with abdominal obesity participated in a lifestyle intervention. MC4R and LCN2 coding regions were screened by Sanger sequencing. Eating behavior was assessed at baseline with the Children Eating Behavior Questionnaire (CEBQ). We detected three previously described non-synonymous MC4R variants (Glu42Lys, Thr150Ile, and Arg305Gln) and one non-synonymous polymorphism (Ile251Leu). Regarding LCN2, one known non-synonymous variant (Thr124Met) was detected. Eating behavior was described in carriers of the MC4R and LCN2 mutation and in non-carriers. MC4R and LCN2 mutations were detected in 2.42% and 0.84%, respectively, of Spanish children with abdominal obesity. A number of subjects with functional mutation variants in MC4R and LCN2 were able to achieve a reduction in BMI-SDS after a lifestyle intervention.

Highlights

Obesity has been defined by the World Health Organization (WHO) as an abnormal or excessive body fat accumulation that may impair health [1]
A total of 112 children between 7 to 16 years of age and with abdominal obesity defined as a waist circumference higher than the 90th percentile [14] participate in a lifestyle intervention
Our study shows a frequency of 2.52% of melanocortin-4 receptor gene (MC4R) mutations leading to a reduced function in our sample of Spanish of children with abdominal obesity

Summary

Introduction

Obesity has been defined by the World Health Organization (WHO) as an abnormal or excessive body fat accumulation that may impair health [1]. Both environmental and genetic factors have an influence on weight gain [2]. One of the most common single genes harboring variants associated with obesity is the melanocortin-4 receptor gene (MC4R) [4,5]. It is known as a regulator of energy homeostasis due to its effect on food intake and energy expenditure via neuronal melanocortinergic pathways [6]. The polymorphism Ile251Leu leads to an increased function of MC4R and is associated with a reduced BMI [7]

Objectives

Methods

Results

Conclusion