Microarray skeletal muscle PGC-1alpha-/- - beta f/f/Mlc1fCre mice

Title: Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin Sensitivity Abstract: Evidence is emerging that the PGC-1 coactivators serve a critical role in skeletal muscle metabolism, function, and disease. Mice with total PGC-1 deficiency in skeletal muscle (PGC-1alpha-/- betaf/f/MLC-Cre mice) were generated and characterized. PGC-1alpha-/-betaf/f/MLC-Cre mice exhibit a dramatic reduction in exercise performance compared to single PGC-1alpha- or PGC-1alpha-deficient mice and wild-type controls. The exercise phenotype of the PGC-1alpha-/-betaf/f/MLC-Cre mice was associated with a marked diminution in muscle oxidative capacity and mitochondrial structural derangements consistent with fusion/fission and biogenic defects together with rapid depletion of muscle glycogen stores during exercise. Surprisingly, the skeletal muscle fiber type profile of the PGC-1alpha-/-betaf/f/MLCCre mice was not significantly different than the wild-type mice. Moreover, insulin sensitivity and glucose tolerance were also not altered in the PGC-1alpha-/-betaf/f/MLC-Cre mice. Taken together, we conclude that PGC-1 coactivators are necessary for the oxidative and mitochondrial programs of skeletal muscle but are dispensable for fundamental fiber type determination and insulin sensitivity. RNA from PGC-1alpha-/- beta f/f/Mlc1fcre was obtained and gene expression pattern compared with PGC-1alpha -/-, PGC-1beta f/f, and PGC-1beta f/f/Mlc1fCre controls. Results file descriptions: 1. GSE23365_skfloxAKO_PPexcl_genesup_GEO-8-16-2010: This table contains genes that were upregulated >=2.0 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column "description" contains the gene name, and the column"ID" contains Agilent probe names. 2. GSE23365_skfloxAKO_PPexcl_genesdown_GEO-8-16-2010 This table contains genes that were downregulated <=0.7 fold in gastrocnemius muscle from PGC-1alpha-/- - mice, PGC-1beta f/f/Mlc1fCre mice and PGC-1alpha-/- - beta f/f/Mlc1fCre mice. All groups are normalized to PGC-1beta f/f mice and values are expressed as mean±SEM. The column "description" contains the gene name, and the column "ID" contains Agilent probe names.标题：骨骼肌总PGC-1缺乏将线粒体紊乱与肌纤维类型决定及胰岛素敏感性解偶联 摘要：越来越多的证据表明，PGC-1共激活因子（PGC-1 coactivators）在骨骼肌代谢、功能及疾病进程中发挥关键调控作用。本研究构建并鉴定了骨骼肌内总PGC-1缺失的小鼠（PGC-1alpha-/- betaf/f/MLC-Cre小鼠）。与单基因敲除的PGC-1alpha-/-小鼠或PGC-1alpha缺失小鼠及野生型对照小鼠相比，该双敲除小鼠的运动能力显著下降。该双敲除小鼠的运动表型与肌肉氧化能力显著降低、线粒体结构紊乱（与融合/分裂及生物发生缺陷相符）以及运动过程中肌糖原储备快速耗竭密切相关。令人意外的是，该双敲除小鼠的骨骼肌肌纤维类型谱与野生型小鼠无显著差异。此外，其胰岛素敏感性及葡萄糖耐量也未发生改变。综上，本研究认为PGC-1共激活因子对骨骼肌的氧化代谢及线粒体相关程序是必需的，但对于基本的肌纤维类型决定及胰岛素敏感性并非不可或缺。 研究人员从PGC-1alpha-/- beta f/f/Mlc1fcre小鼠中提取RNA，并将其基因表达模式与PGC-1alpha -/-、PGC-1beta f/f及PGC-1beta f/f/Mlc1fCre对照小鼠进行对比。 结果文件说明： 1. GSE23365_skfloxAKO_PPexcl_genesup_GEO-8-16-2010：该表格收录了腓肠肌中上调倍数≥2.0的基因，涉及的实验组小鼠包括PGC-1alpha-/-小鼠、PGC-1beta f/f/Mlc1fCre小鼠及PGC-1alpha-/- beta f/f/Mlc1fCre小鼠。所有实验组均以PGC-1beta f/f小鼠作为标准化参照，数据以均值±标准误（mean±SEM）表示。其中“description”列标注基因名称，“ID”列标注安捷伦（Agilent）探针名称。 2. GSE23365_skfloxAKO_PPexcl_genesdown_GEO-8-16-2010：该表格收录了腓肠肌中下调倍数≤0.7的基因，涉及的实验组小鼠包括PGC-1alpha-/-小鼠、PGC-1beta f/f/Mlc1fCre小鼠及PGC-1alpha-/- beta f/f/Mlc1fCre小鼠。所有实验组均以PGC-1beta f/f小鼠作为标准化参照，数据以均值±标准误（mean±SEM）表示。其中“description”列标注基因名称，“ID”列标注安捷伦（Agilent）探针名称。