Bruce Clinton R, Thrush A Brianne, Mertz Valerie A, Bezaire Veronic, Chabowski Adrian, Heigenhauser George J F, Dyck David J
Diabetes and Obesity Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia.
Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E99-E107. doi: 10.1152/ajpendo.00587.2005. Epub 2006 Feb 7.
Muscle fatty acid (FA) metabolism is impaired in obesity and insulin resistance, reflected by reduced rates of FA oxidation and accumulation of lipids. It has been suggested that interventions that increase FA oxidation may enhance insulin action by reducing these lipid pools. Here, we examined the effect of endurance training on rates of mitochondrial FA oxidation, the activity of carnitine palmitoyltransferase I (CPT I), and the lipid content in muscle of obese individuals and related these to measures of glucose tolerance. Nine obese subjects completed 8 wk of moderate-intensity endurance training, and muscle biopsies were obtained before and after training. Training significantly improved glucose tolerance, with a reduction in the area under the curve for glucose (P < 0.05) and insulin (P = 0.01) during an oral glucose tolerance test. CPT I activity increased 250% (P = 0.001) with training and became less sensitive to inhibition by malonyl-CoA. This was associated with an increase in mitochondrial FA oxidation (+120%, P < 0.001). Training had no effect on muscle triacylglycerol content; however, there was a trend for training to reduce both the total diacylglcyerol (DAG) content (-15%, P = 0.06) and the saturated DAG-FA species (-27%, P = 0.06). Training reduced both total ceramide content (-42%, P = 0.01) and the saturated ceramide species (-32%, P < 0.05). These findings suggest that the improved capacity for mitochondrial FA uptake and oxidation leads not only to a reduction in muscle lipid content but also a to change in the saturation status of lipids, which may, at least in part, provide a mechanism for the enhanced insulin action observed with endurance training in obese individuals.
在肥胖和胰岛素抵抗状态下，肌肉脂肪酸（FA）代谢受损，表现为FA氧化速率降低和脂质蓄积。有人提出，增加FA氧化的干预措施可能通过减少这些脂质池来增强胰岛素作用。在此，我们研究了耐力训练对肥胖个体肌肉线粒体FA氧化速率、肉碱棕榈酰转移酶I（CPT I）活性以及脂质含量的影响，并将这些与葡萄糖耐量指标相关联。9名肥胖受试者完成了8周的中等强度耐力训练，并在训练前后进行了肌肉活检。训练显著改善了葡萄糖耐量，口服葡萄糖耐量试验期间葡萄糖曲线下面积（P < 0.05）和胰岛素曲线下面积（P = 0.01）均降低。训练后CPT I活性增加了250%（P = 0.001），且对丙二酰辅酶A抑制的敏感性降低。这与线粒体FA氧化增加（+120%，P < l0.001）相关。训练对肌肉三酰甘油含量无影响；然而，训练有降低总二酰甘油（DAG）含量（-15%，P = 0.06）和饱和DAG-FA种类（-27%，P = 0.06）的趋势。训练降低了总神经酰胺含量（-42%，P = 0.01）和饱和神经酰胺种类（-32%，P < 0.05）。这些发现表明，线粒体FA摄取和氧化能力的提高不仅导致肌肉脂质含量降低，还导致脂质饱和状态的改变，这可能至少部分地为肥胖个体耐力训练后观察到的胰岛素作用增强提供了一种机制。
