Department of Medicine, Division of Endocrinology and Metabolism, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Diabetes. 2011 Oct;60(10):2588-97. doi: 10.2337/db10-1221. Epub 2011 Aug 26.
Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype.
A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies.
DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity.
Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.
尽管慢性运动和肥胖对胰岛素敏感性有相反的影响，但两者都会增加肌内甘油三酯（IMTGs）。我们假设，尽管具有更高的 IMTGs，但经过长期训练的肌肉的骨骼肌二酰基甘油（DAGs）和神经酰胺含量会较低，这可以解释其更高的胰岛素敏感性。我们还假设，参与脂滴水解、DAG 形成以及脂肪酸分配和氧化的关键骨骼肌蛋白的表达与脂毒性表型相关。
共纳入 14 名正常体重的耐力训练运动员（NWA 组）和 7 名正常体重的久坐不动者（NWS 组）和 21 名肥胖的久坐不动者（OBS 组）志愿者。通过葡萄糖钳夹评估胰岛素敏感性。在肌肉活检中测量 IMTGs、DAGs、神经酰胺和蛋白表达。
NWA 组的 DAG 含量比 OBS 组高约两倍，比 NWS 组高约 50%，对应的胰岛素敏感性更高。虽然某些 DAG 部分显然与更好的胰岛素敏感性相关，但其他部分则不然。肥胖胰岛素抵抗肌肉中的神经酰胺含量更高。OXPAT/ perilipin-5、脂肪甘油三酯脂肪酶和硬脂酰辅酶 A 去饱和酶蛋白的表达在 NWA 组更高，与更高的线粒体含量、1 型肌纤维比例、IMTGs、DAGs 和胰岛素敏感性相对应。
高度训练的运动员的总肌细胞 DAG 明显更高，与更高的胰岛素敏感性相对应，这表明 DAG 在胰岛素作用中具有更复杂的作用。我们的数据还为人类提供了更多证据，将神经酰胺与胰岛素抵抗联系起来。最后，本研究为特定骨骼肌蛋白在肌内脂质、线粒体氧化能力和胰岛素抵抗中的作用提供了新的证据。
