Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men
Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men
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DOI：
10.1152/ajpendo.00590.2009
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发表时间：
2010-11-01
影响因子：
5.1
通讯作者：
Vaag, A.
中科院分区：
文献类型：
--
作者：
Alibegovic, A. C.;Sonne, M. P.;Vaag, A.
Alibegovic AC，索内MP，Hojbjerre L，Bork-Jensen J，Jacobsen S，Nilsson E，Faerch K，Hiscock N，Mortensen B，Friedrichsen M，Stallknecht B，Dela F，Vaag A.缺乏运动诱导的胰岛素抵抗与年轻男性骨骼肌中的多种转录变化相关。Am J Physiol Endocrinol Metab 299：E752-E763，2010.首次发表于2010年8月24日; doi：10.1152/ajpendo.00590.2009.-缺乏体力活动是胰岛素抵抗的一个危险因素。我们研究了9天的卧床休息对基础和胰岛素刺激的基因表达的影响，这些基因可能参与胰岛素作用，通过应用假设生成微阵列与候选基因实时PCR方法在20名健康年轻男性中平行进行。此外，我们研究了卧床休息是否影响过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PPARGC 1A）基因启动子区的DNA甲基化。再训练4周后复查受试者。我们发现卧床休息会诱导胰岛素抵抗，并改变了4,500多个基因的表达。这些变化只有部分正常化后4周的再训练。通路分析显示34条通路显著下调，主要是那些与线粒体功能相关的基因，包括PPARGC 1A。尽管诱导胰岛素抵抗，卧床休息导致在一个矛盾的增加响应急性胰岛素刺激的基因的一般表达，特别是那些参与炎症和内质网（ER）的压力。此外，卧床休息改变了几个胰岛素抵抗和糖尿病候选基因的基因表达。我们还观察到卧床休息后PPARGC 1A DNA甲基化增加的趋势。我们的结论是PPARGC 1A和其他参与线粒体功能的基因表达受损，以及炎症和ER应激相关基因对胰岛素的反应增加，可能有助于卧床休息诱导的胰岛素抵抗的发展。缺乏完全正常化的变化后4周的再训练强调了保持最低限度的日常体力活动的重要性。
Alibegovic AC, Sonne MP, Hojbjerre L, Bork-Jensen J, Jacobsen S, Nilsson E, Faerch K, Hiscock N, Mortensen B, Friedrichsen M, Stallknecht B, Dela F, Vaag A. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men. Am J Physiol Endocrinol Metab 299: E752-E763, 2010. First published August 24, 2010; doi: 10.1152/ajpendo.00590.2009.-Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity.