Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans
Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans
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DOI：
10.1152/ajpendo.00142.2017
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发表时间：
2018-02-01
影响因子：
5.1
通讯作者：
EcKel, Robert H.
中科院分区：
文献类型：
--
作者：
Bergman, Bryan C.;Perreault, Leigh;EcKel, Robert H.
肌内甘油三酯（IMTG）浓度在胰岛素抵抗个体中升高，并且一度被认为促进胰岛素抵抗。然而，与患有2型糖尿病的个体相比，接受过糖尿病训练的运动员具有相同的IMTG浓度，并且患糖尿病的风险非常低，称为“运动员悖论”。“我们现在知道IMTG合成与胰岛素敏感性呈正相关，但确切的机制尚不清楚。为了了解IMTG合成与胰岛素敏感性之间的关系，我们测量了肥胖对照组、运动员和2型糖尿病患者在休息、运动和恢复期间的IMTG合成。IMTG合成率与胰岛素敏感性、DAG的胞浆积累以及C18：0神经酰胺和葡萄糖神经酰胺的积累减少呈正相关。运动员的IMTG合成率更高并不能用FFA浓度、DGAT 1 mRNA表达或蛋白质含量的改变来解释。在运动过程中的Ob和T2D的IMTG合成表明利用作为燃料，尽管不变的内容，而IMTG浓度在运动员的运动过程中下降。运动和恢复后，参与脂质去饱和和IMTG合成的基因的mRNA表达增加。此外，在一个子集的个人，运动减少胞质和膜双饱和DAG含量，这可能有助于解释急性运动后的胰岛素敏感化。这些数据表明IMTG合成率可能通过改变细胞内脂质定位和减少促进胰岛素抵抗的特定神经酰胺种类来影响胰岛素敏感性。
Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the "athlete's paradox." We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.