Muscle sn-1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn-1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn-1,2-DAG and ceramide contents by using liquid chromatography-tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn-1,2-DAG and C18:0 ceramide contents after weight loss were not different than values before weight loss. In contrast, mitochondrial/ER C18:0 ceramide content decreased by ∼20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P<0.005). These results suggest a decrease in muscle mitochondrial/ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity.

中文翻译：

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减肥对肥胖和 2 型糖尿病患者骨骼肌生物活性脂质的影响


肌肉 sn-1,2-二酰基甘油 （DAG） 和 C18：0 神经酰胺在肌膜和线粒体区室中的积累已被提出以调节肌肉胰岛素敏感性。在这里，我们评估了减肥诱导的胰岛素敏感性改善是否与肥胖和 2 型糖尿病患者肌肉 sn-1,2-DAG 和神经酰胺含量的变化相关。我们测量了骨骼肌胰岛素敏感性，通过使用高胰岛素-正常血糖钳夹程序结合稳定同位素标记的葡萄糖示踪剂输注进行评估，以及在亚细胞分馏和 DAG 异构体分离后使用液相色谱-串联质谱法评估骨骼肌 sn-1,2-DAG 和神经酰胺含量14 名肥胖和 2 型糖尿病成人患者体重明显减轻前后 （18.6 ± 2.1%）体重减轻。减肥后全身胰岛素敏感性翻了一番。减重后 sarcolemmal sn-1,2-DAG 和 C18：0 神经酰胺含量与减重前无差异。相比之下，减肥后线粒体/ER C18：0 神经酰胺含量下降了 ∼20%（从 2.16 ± 0.08 下降到 1.71 ± 0.13 nmol/g，P<0.005）。这些结果表明，肌肉线粒体/ER C18：0 神经酰胺含量的降低可能有助于减肥对骨骼肌胰岛素敏感性的有益影响。