An acute increase in skeletal muscle carnitine content alters fuel metabolism in resting human skeletal muscle
An acute increase in skeletal muscle carnitine content alters fuel metabolism in resting human skeletal muscle
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DOI：
10.1210/jc.2006-1584
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发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Greenhaff, Paul L.
中科院分区：
文献类型：
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作者：
Stephens, Francis B.;Constantin-Teodosiu, Dumitru;Greenhaff, Paul L.
背景：肉碱在骨骼肌脂肪和碳水化合物的氧化整合中起着至关重要的作用，肥胖和2型糖尿病患者都会受到损害。目的：本研究的目的是探讨骨骼肌总肉碱(TC)含量增加对肌肉燃料代谢的影响。设计：在两次随机试验期间，静脉滴注生理盐水(对照组)或L-卡尼汀5h，同时将血清胰岛素维持在生理浓度。参与者：7名健康的非素食青年(体重指数，26.1+/-1.6 kg/m(2)。主要观察指标：骨骼肌丙酮酸脱氢酶复合体(PDC)活性及相关肌肉代谢物。结果：高卡尼汀血症(600mU/L)和高胰岛素血症(160mU/L)相结合使肌肉TC含量增加15%(P<；与对照组相比，丙酮酸脱氢酶复合体活性(P<；0.05)和肌肉乳酸含量(P<；0.05)分别降低了30%和40%，肌肉糖原(P<；0.01)和长链酰基辅酶A含量(P<；0.05)隔夜分别增加了30%和40%。结论：这些结果表明，在高碳水化合物可利用性的条件下，人体骨骼肌TC含量的急剧增加导致了碳水化合物氧化的抑制，这可能是由于肉碱介导的脂肪氧化的增加。这些新的发现可能对我们理解肌肉脂肪氧化的调节有重要的意义，特别是在运动期间，当肉碱的供应可能限制脂肪氧化时，以及在肥胖症和2型糖尿病已知受损的情况下。
Context: Carnitine plays an essential role in the integration of fat and carbohydrate oxidation in skeletal muscle, which is impaired in obesity and type 2 diabetes.Objective: The aim of the present study was to investigate the effect of an increase in skeletal muscle total carnitine (TC) content on muscle fuel metabolism.Design: A 5-h iv infusion of saline (control) or L-carnitine was administered while serum insulin was maintained at a physiologically high concentration during two randomized visits.Participants: Seven healthy, nonvegetarian young men (body mass index, 26.1 +/- 1.6 kg/m(2)) participated in the present study at the University of Nottingham.Main Outcome Measures: Skeletal muscle pyruvate dehydrogenase complex (PDC) activity and associated muscle metabolites were measured.Results: The combination of hypercarnitinemia (600 mu mol/liter) and hyperinsulinemia (160 mU/liter) increased muscle TC content by 15% (P < 0.01) and was associated with decreased pyruvate dehydrogenase complex activity (P < 0.05) and muscle lactate content (P < 0.05) by 30 and 40%, respectively, and an overnight increase in muscle glycogen (P < 0.01) and long-chain acyl-coenzyme A content (P < 0.05) by 30 and 40%, respectively, compared with control.Conclusions: These results suggest that an acute increase in human skeletal muscle TC content results in an inhibition of carbohydrate oxidation in conditions of high carbohydrate availability, possibly due to a carnitine-mediated increase in fat oxidation. These novel findings may have important implications for our understanding of the regulation of muscle fat oxidation, particularly during exercise, when carnitine availability may limit fat oxidation, and in obesity and type 2 diabetes where it is known to be impaired.