Interaction between an ADCY3 Genetic Variant and Two Weight-Lowering Diets Affecting Body Fatness and Body Composition Outcomes Depending on Macronutrient Distribution: A Randomized Trial.

Leticia Goni,Leticia Goni,Lourdes Ortiz,Fermín I Milagro,Fermín I Milagro,Fermín I Milagro,Fermín I Milagro,Marta Cuervo,Marta Cuervo,Marta Cuervo,Marta Cuervo,Jose Ignacio Riezu-Boj,Jose Ignacio Riezu-Boj,Fernando J Corrales,Fernando J Corrales,Fernando J Corrales,J Alfredo Martínez,J Alfredo Martínez,J Alfredo Martínez,J Alfredo Martínez,J Alfredo Martínez

doi:10.3390/nu10060789

Abstract

The adenylate cyclase 3 (ADCY3) gene is involved in the regulation of several metabolic processes including the development and function of adipose tissue. The effects of the ADCY3 rs10182181 genetic variant on changes in body composition depending on the macronutrient distribution intake after 16 weeks of the dietary intervention were tested. The ADCY3 genetic variant was genotyped in 147 overweight or obese subjects, who were randomly assigned to one of the two diets varying in macronutrient content: a moderately-high-protein diet and a low-fat diet. Anthropometric and body composition measurements (DEXA scan) were recorded. Significant interactions between the ADCY3 genotype and dietary intervention on changes in weight, waist circumference, and body composition were found after adjustment for covariates. Thus, in the moderately-high-protein diet group, the G allele was associated with a lower decrease of fat mass, trunk and android fat, and a greater decrease in lean mass. Conversely, in the low-fat diet group carrying the G allele was associated with a greater decrease in trunk, android, gynoid, and visceral fat. Subjects carrying the G allele of the rs10182181 polymorphism may benefit more in terms of weight loss and improvement of body composition measurements when undertaking a hypocaloric low-fat diet as compared to a moderately-high-protein diet.

Highlights

Obesity is a multifactorial disease in which various pathophysiological processes are involved, including the hormonal regulation of hunger and satiety, the activity of the central reward system, whole-body energy expenditure and the storage capacity for fat in the adipose tissue, and interactions with environmental factors [1]
The current study reported for the first time a significant gene–diet interaction between adenylate cyclase 3 (ADCY3)
The ADCY3 gene encodes for an enzyme that converts the adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which is a second messenger used for intracellular signal transduction [3]

Summary

Introduction

Obesity is a multifactorial disease in which various pathophysiological processes are involved, including the hormonal regulation of hunger and satiety, the activity of the central reward system, whole-body energy expenditure and the storage capacity for fat in the adipose tissue, and interactions with environmental factors [1]. In each of these metabolic functions a set of genes is implicated, Nutrients 2018, 10, 789; doi:10.3390/nu10060789 www.mdpi.com/journal/nutrients. Among the ADCY3 genetic variants identified as related to obesity traits, the polymorphism rs10182181 has been replicated in the largest meta-analysis of GWAS on body mass index (BMI) carried out to date [12]

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