Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, 7505, South Africa.
Division of Medical Physiology, Centre for Cardiometabolic Research in Africa (CARMA), Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, 7505, South Africa.
Sci Rep. 2022 Jul 11;12(1):11771. doi: 10.1038/s41598-022-15678-6.
We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.
我们研究了肥胖非洲女性接受 12 周干预后，FKBP5 的臀肌 (GSAT) 和腹部皮下脂肪组织 (ASAT) DNA 甲基化情况，以及 rs1360780 单核苷酸多态性 (SNP) 对 FKBP5 甲基化、基因表达和肥胖及代谢相关参数的运动后训练适应的影响。运动 (n = 19) 组参与者接受了 12 周的监督性有氧运动和抗阻训练，而对照组 (n = 12) 则继续保持他们的日常行为。使用焦磷酸测序法测量 GSAT 和 ASAT 中的 FKBP5 甲基化。使用定量实时 PCR 进行 SNP 和基因表达分析。运动训练导致第 7 内含子内两个 CpG 二核苷酸处的 FKBP5 过度甲基化。当根据 rs1360780 SNP 进行分层时，CT 基因型的参与者在 GSAT 中显示 FKBP5 过度甲基化 (p < 0.05)，而在 CC 和 CT 携带者中显示 ASAT 过度甲基化。CC 等位基因携带者在运动训练后表现出心肺功能适应性提高、胰岛素敏感性提高、女性型脂肪质量增加和腰围减小 (p < 0.05)，而 CT 基因型的女性这些参数减弱。这些发现为未来更大队列的研究提供了基础，应该评估 FKBP5 甲基化和/或遗传变异（如 rs1360780 SNP）是否对运动干预的反应有重大影响。
