Federal Research Centre for Nutrition and Food, Max-Rubner-Institut, Kiel, Germany,
Genes Nutr. 2012 Jul;7(3):437-45. doi: 10.1007/s12263-012-0280-z. Epub 2012 Jan 24.
The fatty-acid-binding protein-2 (FABP2) gene has been proposed as a candidate gene for diabetes because the encoded protein is involved in fatty acid absorption and therefore may affect insulin sensitivity and glucose metabolism. The rare haplotype (B) of its promoter was shown to be associated with a lower risk for type 2 diabetes. The aim of this study was to investigate whether a polymorphism in the FABP2 promoter does affect the metabolic response to either an medium-chain triacylglycerol (MCT) or an long-chain triacylglycerol (LCT) diet, which were suggested to differ in transport mechanisms, in affinity to FABP2, in activating transcription factors binding to the FABP2 promoter and in their effects on insulin sensitivity. We studied 82 healthy male subjects varying in the FABP2 promoter (42 homozygous for common haplotype (A), 40 homozygous for the rare haplotype (B)) in an interventional study with either an MCT or LCT diet over 2 weeks to examine gene-nutrient interaction. The saturation grade of MCT was adjusted to that of the LCT fat. We determined glucose, insulin, triacylglycerols (TGs), chylomicron triacylglycerols and cholesterol before and after a standardised mixed meal before and after the intervention. HDL cholesterol increased in all groups, which was most pronounced in subjects homozygous for the common promoter haplotype A who received MCT diet (P = 0.001), but not significant in homozygous rare haplotype B subjects who received MCT fat. Subjects homozygous for FABP2 haplotype A showed a significant decrease in fasting and postprandial glucose (P = 0.01, 0.04, respectively) and a decrease in insulin resistance (HOMA-IR, P = 0.04) during LCT diet. After correction for multiple testing, those effects did not remain significant. Fasting and postprandial triacylglycerols, LDL cholesterol, chylomicron TGs and cholesterol were not affected by genotype or diet. MCT diet increased HDL cholesterol dependent on the FABP2 promoter haplotype. The effects of the promoter haplotype B could be mediated by PPARγ, which is upregulated by medium-chain fatty acids.
脂肪酸结合蛋白-2（FABP2）基因被认为是糖尿病的候选基因，因为其编码的蛋白参与脂肪酸吸收，因此可能影响胰岛素敏感性和葡萄糖代谢。其启动子的罕见单倍型（B）与 2 型糖尿病的风险降低相关。本研究旨在探讨 FABP2 启动子的多态性是否会影响中链三酰甘油（MCT）或长链三酰甘油（LCT）饮食的代谢反应，因为这两种饮食的转运机制、与 FABP2 的亲和力、激活转录因子结合 FABP2 启动子的能力以及对胰岛素敏感性的影响不同。我们在一项干预性研究中研究了 82 名健康男性，他们的 FABP2 启动子存在多态性（42 名纯合子常见单倍型（A），40 名纯合子罕见单倍型（B）），在 2 周内分别给予 MCT 或 LCT 饮食，以检查基因-营养相互作用。MCT 的饱和度等级调整为 LCT 脂肪的饱和度等级。我们在干预前后测定了标准混合餐后空腹和餐后的葡萄糖、胰岛素、三酰甘油（TGs）、乳糜微粒三酰甘油和胆固醇。所有组的 HDL 胆固醇均升高，其中接受 MCT 饮食的纯合常见启动子单倍型 A 受试者最为明显（P=0.001），但接受 MCT 脂肪的纯合罕见单倍型 B 受试者则不明显。FABP2 单倍型 A 纯合子受试者在接受 LCT 饮食时，空腹和餐后血糖显著降低（P=0.01，0.04），胰岛素抵抗（HOMA-IR）降低（P=0.04）。经过多次检验校正后，这些影响不再显著。基因型或饮食对空腹和餐后 TGs、LDL 胆固醇、乳糜微粒 TGs 和胆固醇均无影响。MCT 饮食增加 HDL 胆固醇，依赖于 FABP2 启动子单倍型。启动子单倍型 B 的影响可能通过过氧化物酶体增殖物激活受体γ（PPARγ）介导，而中链脂肪酸可上调 PPARγ。
