丙酮酸脱氢酶磷酸酶调节基因表达与运动训练引起的胰岛素敏感性变化相关。
Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes.
作者信息
Barberio Matthew D, Huffman Kim M, Giri Mamta, Hoffman Eric P, Kraus William E, Hubal Monica J
机构信息
1Research Center for Genetic Medicine, Children's National Medical Center, Durham, NC; 2Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC; 3Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC; 4Department of Exercise and Nutrition Sciences, George Washington University, WASHINGTON, DC; 5Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC; and 6Department of Integrative Systems Biology, George Washington University, Washington, DC.
出版信息
Med Sci Sports Exerc. 2016 Dec;48(12):2387-2397. doi: 10.1249/MSS.0000000000001041.
PURPOSE
Whole body insulin sensitivity (Si) typically improves after aerobic exercise training; however, individual responses can be highly variable. The purpose of this study was to use global gene expression to identify skeletal muscle genes that correlate with exercise-induced Si changes.
METHODS
Longitudinal cohorts from the Studies of Targeted Risk Reduction Intervention through Defined Exercise were used as Discovery (Affymetrix) and Confirmation (Illumina) of vastus lateralis gene expression profiles. Discovery (n = 39; 21 men) and Confirmation (n = 42; 19 men) cohorts were matched for age (52 ± 8 vs 51 ± 10 yr), body mass index (30.4 ± 2.8 vs 29.7 ± 2.8 kg·m), and V˙O2max (30.4 ± 2.8 vs 29.7 ± 2.8 mL·kg·min). Si was determined via intravenous glucose tolerance test pretraining and posttraining. Pearson product-moment correlation coefficients determined relationships between a) baseline and b) training-induced changes in gene expression and %ΔSi after training.
RESULTS
Expression of 2454 (Discovery) and 1778 genes (Confirmation) at baseline were significantly (P < 0.05) correlated to %ΔSi; 112 genes overlapped. Pathway analyses identified Ca signaling-related transcripts in this 112-gene list. Expression changes of 1384 (Discovery) and 1288 genes (Confirmation) after training were significantly (P < 0.05) correlated to %ΔSi; 33 genes overlapped, representing contractile apparatus of skeletal and smooth muscle genes. Pyruvate dehydrogenase phosphatase regulatory subunit expression at baseline (P = 0.01, r = 0.41) and posttraining (P = 0.01, r = 0.43) were both correlated with %ΔSi.
CONCLUSIONS
Exercise-induced adaptations in skeletal muscle Si are related to baseline levels of Ca-regulating transcripts, which may prime the muscle for adaptation. Relationships between %ΔSi and pyruvate dehydrogenase phosphatase regulatory, a regulatory subunit of the pyruvate dehydrogenase complex, indicate that the Si response is strongly related to key steps in metabolic regulation.
目的
有氧运动训练后，全身胰岛素敏感性（Si）通常会提高；然而，个体反应可能存在很大差异。本研究的目的是利用全基因组表达来确定与运动诱导的Si变化相关的骨骼肌基因。
方法
来自通过明确运动进行靶向风险降低干预研究的纵向队列被用作外侧股四头肌基因表达谱的发现队列（Affymetrix）和验证队列（Illumina）。发现队列（n = 39；21名男性）和验证队列（n = 42；19名男性）在年龄（52±8岁对51±10岁）、体重指数（30.4±2.8对29.7±2.8 kg·m²）和最大摄氧量（30.4±2.8对29.7±2.8 mL·kg⁻¹·min⁻¹）方面相匹配。通过训练前和训练后的静脉葡萄糖耐量试验来测定Si。Pearson积差相关系数确定了a）基线与b）训练诱导的基因表达变化与训练后%ΔSi之间的关系。
结果
基线时2454个基因（发现队列）和1778个基因（验证队列）的表达与%ΔSi显著相关（P < 0.05）；有112个基因重叠。通路分析在这112个基因列表中确定了与钙信号相关的转录本。训练后1384个基因（发现队列）和1288个基因（验证队列）的表达变化与%ΔSi显著相关（P < 0.05）；有33个基因重叠，代表骨骼肌和平滑肌的收缩装置基因。基线时（P = 0.01，r = 0.41）和训练后（P = 0.01，r = 0.43）丙酮酸脱氢酶磷酸酶调节亚基的表达均与%ΔSi相关。
结论
运动诱导的骨骼肌Si适应性变化与钙调节转录本的基线水平有关，这可能使肌肉为适应做好准备。%ΔSi与丙酮酸脱氢酶磷酸酶调节亚基（丙酮酸脱氢酶复合体的一个调节亚基）之间的关系表明，Si反应与代谢调节的关键步骤密切相关。
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