The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with Type 2 diabetes (T2D). We hypothesize that 10 wk of supervised endurance training improves SKM mitochondrial function and insulin sensitivity that are related to alterations in lipid signatures within SKM of T2D (males n = 8). We employed integrated multi-omics data analyses including ex vivo lipidomics (MS/MS-shotgun) and transcriptomics (RNA-Seq). From biopsies of SKM, tissue and primary myotubes mitochondrial respiration were quantified by high-resolution respirometry. We also performed hyperinsulinemic-euglycemic clamps and blood draws before and after the training. The lipidomics analysis revealed that endurance training (>95% compliance) increased monolysocardiolipin by 68.2% (P ≤ 0.03), a putative marker of mitochondrial remodeling, and reduced total sphingomyelin by 44.8% (P ≤ 0.05) and phosphatidylserine by 39.7% (P ≤ 0.04) and tended to reduce ceramide lipid content by 19.8%. Endurance training also improved intrinsic mitochondrial respiration in SKM of T2D without alterations in mitochondrial DNA copy number or cardiolipin content. RNA-Seq revealed 71 transcripts in SKM of T2D that were differentially regulated. Insulin sensitivity was unaffected, and HbA1c levels moderately increased by 7.3% despite an improvement in cardiorespiratory fitness (V̇o2peak) following the training intervention. In summary, endurance training improves intrinsic and cell-autonomous SKM mitochondrial function and modifies lipid composition in men with T2D independently of alterations in insulin sensitivity and glycemic control.

中文翻译：

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耐力训练可重塑2型糖尿病男性的骨骼肌磷脂组成，并增加内在的线粒体呼吸。

运动训练对骨骼肌（SKM）脂质组和线粒体功能的影响尚未在2型糖尿病（T2D）患者中进行深入研究。我们假设10周的有监督耐力训练可改善SKM线粒体功能和胰岛素敏感性，这与T2D的SKM内脂质特征的改变有关（男性n = 8）。我们采用了综合的多组学数据分析，包括离体脂质组学（MS / MS-shotgun）和转录组学（RNA-Seq）。从SKM活检中，组织和原代肌管的线粒体呼吸通过高分辨率呼​​吸测定法进行定量。在训练前后，我们还进行了高胰岛素-正常血糖钳夹和抽血。脂质组学分析显示，耐力训练（> 95％依从性）使单糖心磷脂增加68.2％（P≤0.03），线粒体重塑的可能标志物，总鞘磷脂减少44.8％（P≤0.05），磷脂酰丝氨酸减少39.7％（P≤0.04），并且神经酰胺脂质含量减少19.8％。耐力训练还可以改善T2D的SKM中固有的线粒体呼吸，而不会改变线粒体DNA拷贝数或心磷脂含量。RNA-Seq揭示了T2D的SKM中有71个转录物受到差异调节。胰岛素敏感性未受影响，尽管在训练干预后心肺适应性（V̇o2peak）有所改善，HbA1c水平仍温和增加了7.3％。总之，耐力训练可改善T2D男性的内在和细胞自主性SKM线粒体功能，并改变其脂质组成，而与胰岛素敏感性和血糖控制的改变无关。