<b><i>FTO</i></b> Genotype Interacts with Improvement in Aerobic Fitness on Body Weight Loss During Lifestyle Intervention

Abstract

Objective: Not every participant responds with a comparable body weight loss to lifestyle intervention, despite the same compliance. Genetic factors may explain parts of this difference. Variation in fat mass and obesity-associated gene (FTO) is the strongest common genetic determinant of body weight. The aim of the present study was to evaluate the impact of FTO genotype differences in the link between improvement of fitness and reduction of body weight during a lifestyle intervention. Methods: We genotyped 292 healthy subjects for FTO rs8050136. Participants underwent a 9-month lifestyle intervention. Before and after intervention, aerobic fitness was tested by bicycle (VO₂max) and treadmill spiroergometry (individual anaerobic threshold (IAT), subgroup of N = 192). Results: Participants lost body weight (p < 0.0001) independent of FTO genotype (p = 0.5). There was a significant correlation between improvement in VO₂max and decrease in body weight (p < 0.0001). FTO genotype interacted with this relationship (p = 0.0042 for VO₂max, p = 0.0049 for IAT). When stratifying the cohort according to their improvement in VO₂max, FTO obesity-risk A-allele carriers in the higher quartiles of improvement in fitness lost significantly less body weight. Conclusions: Our data reveal that genetic variation in FTO impacts on body weight reduction during lifestyle intervention only in subjects with marked improvement in aerobic fitness.

A fat mass and obesity-associated gene polymorphism influences fat mass in exercise-trained individuals

“…Previous work has shown that exercise intervention can ameliorate the influence of FTO risky alleles on BMI on the FTO rs8050136 SNP [ 8 , 9 ] and the rs9939609 SNP [ 10 – 12 ]. However, due to the direct influence of the FTO SNP rs1421085 on early adipocyte differentiation, the effect of exercise training on body fat in the risky allele carriers of the rs1421085 SNP are less certain.…”

The sex‐specific influence of FTO genotype on exercise intervention for weight loss in adult with obesity

“…Xiang et al carried out a systematic review and meta‐analysis confirming the association between the FTO rs9939609 risk allele and greater weight loss in response to diet/lifestyle interventions (Xiang et al, 2016). Among healthy subjects, after 9 months of lifestyle intervention, there was no statistically significant difference between genotype for the obesity risk variant in FTO (Sailer et al, 2016). Collectively, the conflicting results mentioned above may be ascribed to the study design, exercise programme, race and gender.…”

FTO and Anthropometrics: The Role of Modifiable Factors

“…The aforementioned studies suggest that physical activity plays a role in regulating FTO gene expression. It is worth noting that both Wang et al and Sailer et al [ 35 ] reported greater response to exercise in risk allele groups. This seems counterintuitive because the propensity to be overweight or obese is attributed to the risk alleles.…”

“…Sailer et al [ 35 ] examined subject’s response to exercise as it related to FTO genotype. Subjects underwent a 9-month lifestyle intervention that included 3 h of moderate physical exercise per week and monthly sessions with a dietary counselor.…”

“…Interestingly, the greatest improvements in VO2Max were exhibited by the risk allele group. This study did not instruct subjects to reduce energy intake; therefore, it is not surprising that subjects did not lose a significant amount of weight [ 35 ]. The authors do not offer an explanation as to why the risk allele showed the greatest improvements in exercise capacity…”