Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans

Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans
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DOI:
10.1007/s00125-015-3850-y
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发表时间:
2016-04-01
期刊:
影响因子:
8.2
通讯作者:
Perreault, Leigh
Perreault, Leigh
中科院分区:
医学1区
文献类型:
--
作者:
Bergman, Bryan C.;Brozinick, Joseph T.;Perreault, Leigh

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目的/假设神经酰胺和其他鞘脂包括在骨骼肌中蓄积并促进胰岛素抵抗的脂质分子家族。慢性耐力运动训练降低了肌肉神经酰胺和其他鞘脂,但对单次运动的影响知之甚少。(1.5小时,50%(v)超过dotO(2 max))和恢复对肥胖志愿者、耐力训练运动员和2型糖尿病患者肌肉鞘脂含量的影响。0神经酰胺(p = 0.029)、二氢神经酰胺(p = 0.06)和葡萄糖神经酰胺(p = 0.03)与胰岛素敏感性呈负相关,而总神经酰胺、二氢神经酰胺和葡萄糖神经酰胺浓度无差异。肌肉C18:0二氢神经酰胺与肌肉炎症标志物相关(p = 0.04)。编码鞘脂合成酶的基因在运动员中的转录更高,表明鞘脂合成能力增加。肌肉神经酰胺和鞘脂的总浓度增加,在运动过程中,然后恢复后下降,在此期间,神经酰胺水平降低到显着低于基础水平。结论/解释这些数据表明,神经酰胺和其他鞘脂含有硬脂酸酯(18:0)是唯一相关的骨骼肌胰岛素抵抗。从运动恢复后肌肉神经酰胺浓度降低;这可能是一种促进急性运动胰岛素增敏作用的机制。
Aims/hypotheses Ceramides and other sphingolipids comprise a family of lipid molecules that accumulate in skeletal muscle and promote insulin resistance. Chronic endurance exercise training decreases muscle ceramides and other sphingolipids, but less is known about the effects of a single bout of exercise.Methods We measured basal relationships and the effect of acute exercise (1.5 h at 50% (v) over dotO(2max)) and recovery on muscle sphingolipid content in obese volunteers, endurance trained athletes and individuals with type 2 diabetes.Results Muscle C18:0 ceramide (p = 0.029), dihydroceramide (p = 0.06) and glucosylceramide (p = 0.03) species were inversely related to insulin sensitivity without differences in total ceramide, dihydroceramide, and glucosylceramide concentration. Muscle C18:0 dihydroceramide correlated with markers of muscle inflammation (p = 0.04). Transcription of genes encoding sphingolipid synthesis enzymes was higher in athletes, suggesting an increased capacity for sphingolipid synthesis. The total concentration of muscle ceramides and sphingolipids increased during exercise and then decreased after recovery, during which time ceramide levels reduced to significantly below basal levels.Conclusions/interpretation These data suggest ceramide and other sphingolipids containing stearate (18:0) are uniquely related to insulin resistance in skeletal muscle. Recovery from an exercise bout decreased muscle ceramide concentration; this may represent a mechanism promoting the insulin-sensitising effects of acute exercise.