Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

Stefan G.J.A Camps,Freek G Bouwman,Klaas R Westerterp,Sanne P.M Verhoef,Edwin C.M Mariman

doi:10.1016/j.gene.2019.100019

Abstract

BackgroundEnergy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs).Methods148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters.ResultsThe heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62–1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40–1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39–1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss.ConclusionCarrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.

Highlights

The increasing prevalence of obesity and its comorbidities is one of the major health problems in our modern world (Catenacci et al., 2009)
The present study shows that obese men and women homozygous for the minor ADRB2 rs1042713 allele (AA) show a larger energy restriction induced adaptation in resting energy expenditure (REE) or adaptive thermogenesis
Subjects carrying the heterozygotic genotype of fat mass and obesity associated (FTO) rs9939609 had higher physical activity at baseline and this was carried over after weight loss

Summary

Introduction

The increasing prevalence of obesity and its comorbidities is one of the major health problems in our modern world (Catenacci et al., 2009). Several studies have demonstrated a decrease in physical activity and activity induced energy expenditure (AEE) as a result from weight loss (Martin et al, 2007; Camps et al, 2013; de Groot et al, 1989; Velthuis-te Wierik et al, 1995; Redman et al, 2009; Bonomi et al, 2013). These two metabolic adaptations can limit weight loss and can be important factors that compromise the maintenance of a reduced body weight.

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