Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy.
J Clin Endocrinol Metab. 2019 Apr 1;104(4):1119-1130. doi: 10.1210/jc.2018-01820.
Structured exercise programs are of great benefit for the treatment of type 2 diabetes (T2DM). However, whether aerobic (AER) or resistance (RES) exercise training exerts specific epigenetic changes through the expression profile of circulating miRNAs (c-miRNAs) is still largely unknown.
To assess whether the c-miRNAs profile changes after either AER or RES training in subjects with T2DM.
Twenty-four patients with T2DM randomized to AER or RES training protocols were randomly selected from the Resistance vs. Aerobic Exercise in Type 2 Diabetes (RAED2) Trial (NAER = 12; NRES = 12). The baseline and post-training levels of 179 c-miRNAs were initially measured by RT-PCR in 6 individuals (NAER = 3; NRES = 3). C-miRNAs exhibiting ≥40% fold change variation and/or nominal significance from baseline were measured in the whole group.
Nineteen c-miRNAs were eventually assessed in the whole group. Compared with baseline, the post-training levels of miR-423-3p, miR-451a, and miR-766-3p were significantly up-regulated, irrespective of exercise type (P < 0.0026; 0.05/19), and targeted upstream pathways relevant to fatty acids biosynthesis and metabolic regulation. MiR-451a and miR-423-3p were significantly correlated with fat loss (ρ = 0.45 and 0.43, respectively) and resulted, alone or in combination, in being predictors of fat loss in generalized linear regression models including exercise type as covariate. Only the association with miR-451a eventually retained significance after further correction for age, sex, body mass index, and HbA1c.
Exercise training in T2DM is associated with substantial c-miRNAs profile changes, irrespective of exercise type and other relevant metabolic covariates. The mechanistic significance of the observed relationship between fat loss and the epigenetic modifications induced by exercise warrants further investigation in larger datasets.
有规律的运动对 2 型糖尿病（T2DM）的治疗有很大益处。然而，有氧运动（AER）或抗阻运动（RES）训练是否通过循环 microRNA（c-miRNA）的表达谱发挥特定的表观遗传变化仍知之甚少。
评估 T2DM 患者接受 AER 或 RES 训练后 c-miRNA 谱是否发生变化。
从 2 型糖尿病抗阻与有氧运动（RAED2）试验（NAER = 12；NRES = 12）中随机选择 24 名 T2DM 患者，随机分为 AER 或 RES 训练方案。在 6 名个体中（NAER = 3；NRES = 3），通过 RT-PCR 最初测量了基线和训练后的 179 个 c-miRNA 水平。在整个组中测量了表现出≥40%的折叠变化和/或与基线相比有显著差异的 c-miRNA。
最终在整个组中评估了 19 个 c-miRNA。与基线相比，miR-423-3p、miR-451a 和 miR-766-3p 的训练后水平显著上调，与运动类型无关（P < 0.0026；0.05/19），并靶向与脂肪酸生物合成和代谢调节相关的上游途径。miR-451a 和 miR-423-3p 与脂肪量减少显著相关（ρ分别为 0.45 和 0.43），单独或组合，在包括运动类型作为协变量的广义线性回归模型中，是脂肪量减少的预测因子。只有与 miR-451a 的相关性在进一步校正年龄、性别、体重指数和 HbA1c 后仍然具有统计学意义。
T2DM 患者接受运动训练后，c-miRNA 谱发生显著变化，与运动类型和其他相关代谢因素无关。在更大的数据集进一步研究运动引起的表观遗传改变与脂肪量减少之间的观察到的关系的机制意义是必要的。
