Supplementary Material for: FTO Genotype Interacts with Improvement in Aerobic Fitness on Body Weight Loss During Lifestyle Intervention

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.

研究目的：尽管依从性一致，但并非所有参与者在生活方式干预中均能获得相当程度的体重减轻。遗传因素或可部分解释这一差异。脂肪量与肥胖相关基因（fat mass and obesity-associated gene, FTO）的变异是影响体重的最强常见遗传决定因素。本研究旨在评估生活方式干预期间，FTO基因型差异对有氧适能改善与体重减轻二者关联的调控作用。
研究方法：我们对292名健康受试者进行了FTO rs8050136位点的基因分型。所有参与者均接受为期9个月的生活方式干预。干预前后，受试者的有氧适能通过两种方式评估：自行车运动心肺试验检测最大摄氧量（VO₂max）；跑台运动心肺试验检测个体无氧阈值（individual anaerobic threshold, IAT），该检测的亚组样本量为192例。
研究结果：无论FTO基因型如何，参与者均出现体重减轻（p < 0.0001），且该效应与FTO基因型无显著关联（p = 0.5）。VO₂max提升幅度与体重降低幅度呈显著正相关（p < 0.0001）。FTO基因型与该关联存在显著交互作用（VO₂max维度p = 0.0042，IAT维度p = 0.0049）。当根据VO₂max提升幅度对队列进行分层分析后，在有氧适能提升幅度较高的四分位组中，携带FTO肥胖风险A等位基因的受试者体重减轻程度显著更低。
研究结论：本研究数据显示，仅在有氧适能出现显著提升的受试者中，FTO基因变异会影响生活方式干预期间的体重减轻效果。