Zheng Yan, Huang Tao, Zhang Xiaomin, Rood Jennifer, Bray George A, Sacks Frank M, Qi Lu
Department of Nutrition, Harvard School of Public Health, Boston, MA;
Department of Occupational and Environmental Health and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
J Nutr. 2015 May;145(5):977-82. doi: 10.3945/jn.115.210005. Epub 2015 Mar 11.
The common variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and insulin resistance. Recently, studies also linked FTO variants with macronutrient intakes.
We aimed to investigate whether diet interventions varying in macronutrients modified the effects of FTO genotypes on changes in insulin resistance.
We genotyped FTO variants rs1558902 and rs9939609 and measured insulin resistance in fasting plasma samples at baseline and at 6-mo and 2-y visits in 743 overweight or obese adults (aged 30-70 y, 60% women) from a randomized weight-loss dietary interventional trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. We assessed interactions between FTO variants and intakes of dietary fat and protein in relation to change in body weight and insulin resistance using generalized estimating equation models.
We found significant interactions between rs1558902 and dietary fat on changes in homeostasis model assessment of insulin resistance (HOMA-IR) and insulin (P = 0.003 and 0.004, respectively). Each risk allele (A) of rs1558902 showed a trend to be related to a 0.05-unit less reduction in both log(insulin) and log(HOMA-IR) among the participants assigned to low-fat diets (both P = 0.06), but this was not significantly related to reduction in those assigned to high-fat diets (both P > 0.1) during the 2-y period of intervention. Our data showed that the association between rs9939609 and changes in insulin resistance was not modified by diet macronutrient intakes.
Our results show that carriers of the risk alleles of rs1558902 benefit differently in improving insulin sensitivity by consuming high-fat weight-loss diets rather than low-fat diets. Still, given our data, we acknowledge it is difficult to determine whether fat or carbohydrate contributed to the observed associations.
脂肪量和肥胖相关（FTO）基因的常见变异与肥胖和胰岛素抵抗有关。最近，研究还将FTO变异与常量营养素摄入联系起来。
我们旨在研究不同常量营养素的饮食干预是否会改变FTO基因型对胰岛素抵抗变化的影响。
我们对743名超重或肥胖成年人（年龄30 - 70岁，60%为女性）进行了FTO变异rs1558902和rs9939609的基因分型，并在一项随机减肥饮食干预试验“运用新型饮食策略预防超重（POUNDS LOST）试验”的基线、6个月和2年随访时测量空腹血浆样本中的胰岛素抵抗。我们使用广义估计方程模型评估FTO变异与膳食脂肪和蛋白质摄入量之间关于体重和胰岛素抵抗变化的相互作用。
我们发现rs1558902与膳食脂肪在胰岛素抵抗稳态模型评估（HOMA - IR）和胰岛素变化方面存在显著相互作用（分别为P = 0.003和0.004）。在接受低脂饮食的参与者中，rs1558902的每个风险等位基因（A）显示出与log(胰岛素)和log(HOMA - IR)降低幅度减少0.05单位相关的趋势（P均 = 0.06），但在2年干预期间，这与接受高脂饮食参与者的降低幅度无显著相关（P均>0.1）。我们的数据表明，rs9939609与胰岛素抵抗变化之间的关联未因饮食常量营养素摄入而改变。
我们的结果表明，rs1558902风险等位基因携带者通过食用高脂减肥饮食而非低脂饮食在改善胰岛素敏感性方面获益不同。不过，根据我们的数据，我们承认难以确定是脂肪还是碳水化合物导致了观察到的关联。
