Caloric restriction (CR) improves markers of aging in humans; but it is not known if the fat mass and obesity-associated gene (FTO) rs9939609 single nucleotide polymorphism (SNP), which is associated with appetite and energy intake, influences adherence to prolonged CR. Utilizing data from the two-year Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 randomized controlled trial, we tested whether the FTO rs9939609 SNP was associated with adherence to CR in healthy adults without obesity. As secondary aims, we assessed whether the FTO rs9939609 SNP was associated with changes in body composition, biomarkers of aging, and eating behaviors. Participants were randomized into either a CR group that targeted a 25% reduction in energy intake compared to the habitual energy intake at baseline, or an ad libitum (AL) control group. Participants were genotyped for the FTO rs9939609 SNP. Dietary adherence was determined through changes in energy intake using doubly labeled water and changes in body composition at baseline, month 12, and month 24 in both the CR and AL condition. Weight, body composition, resting metabolic rate (RMR), adiponectin, insulin, leptin, and eating behaviors were measured at the same timepoints. A total of 144 participants (91 CR and 53 AL, age: 38.6 ± 7.1 years; body mass index: 25.3 ± 1.7 kg/m²) were studied. Of these, 27 were homozygous for the ‘obesity-risk’ A allele (AA), while 44 were homozygous for the T allele (TT) and 73 were heterozygotes (AT). By design, the CR group exhibited greater percent CR compared to the AL group during the trial (P < 0.01), but no genotype-by-treatment interaction was observed for change in energy intake or percent CR (P ≥ 0.40). The FTO rs9939609 SNP was also negligibly associated with change in most other endpoints (P ≥ 0.13), though AAs showed a reduction in RMR adjusted for body composition change over the 24 months relative to TTs (genotype-by-treatment interaction: P = 0.03). In a two-year CR intervention delivered to healthy individuals without obesity, the FTO rs9939609 SNP was not associated with adherence to CR and did not alter improvements in most aging biomarkers.

热量限制 (CR) 可改善人类衰老指标；但尚不清楚与食欲和能量摄入相关的脂肪量和肥胖相关基因 ( FTO ) rs9939609 单核苷酸多态性 (SNP) 是否会影响对延长 CR 的依从性。利用为期两年的减少能量摄入的长期影响综合评估 (CALERIE™) 2 期随机对照试验的数据，我们测试了FTO rs9939609 SNP 是否与健康成人无肥胖症的 CR 依从性相关。作为次要目标，我们评估了FTO是否rs9939609 SNP 与身体成分、衰老的生物标志物和饮食行为的变化有关。参与者被随机分配到一个 CR 组，与基线时的习惯性能量摄入相比，目标是减少 25% 的能量摄入，或一个随意 (AL) 对照组。参与者对FTO rs9939609 SNP 进行基因分型。在 CR 和 AL 条件下，通过使用双重标记水的能量摄入变化和基线、第 12 个月和第 24 个月的身体成分变化来确定饮食依从性。在相同的时间点测量体重、身体成分、静息代谢率 (RMR)、脂联素、胰岛素、瘦素和饮食行为。共有 144 名参与者（91 名 CR 和 53 名 AL，年龄：38.6 ± 7.1 岁；体重指数：25.3 ± 1.7 kg/m ²) 进行了研究。其中，27 个是“肥胖风险”A 等位基因 (AA) 的纯合子，而 44 个是 T 等位基因 (TT) 的纯合子，73 个是杂合子 (AT)。根据设计，在试验期间，CR 组的 CR 百分比高于 AL 组（P  < 0.01），但没有观察到能量摄入或 CR 百分比的基因型与治疗之间的相互作用（P  ≥ 0.40）。FTO rs9939609 SNP 与大多数其他终点的变化也可忽略不计（P ≥  0.13），尽管 AA 显示 RMR 在 24 个月内相对于 TT 的身体成分变化调整后降低（基因型-治疗相互作用：P = 0.03)。在对没有肥胖的健康个体进行的为期两年的 CR 干预中，FTO rs9939609 SNP 与 CR 的依从性无关，也没有改变大多数衰老生物标志物的改善。