Stephens Francis B, Constantin-Teodosiu Dumitru, Laithwaite David, Simpson Elizabeth J, Greenhaff Paul L
Centre for Integrated Systems Biology and Medicine, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
J Clin Endocrinol Metab. 2006 Dec;91(12):5013-8. doi: 10.1210/jc.2006-1584. Epub 2006 Sep 19.
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.
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.
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.
Seven healthy, nonvegetarian young men (body mass index, 26.1 +/- 1.6 kg/m2) participated in the present study at the University of Nottingham.
Skeletal muscle pyruvate dehydrogenase complex (PDC) activity and associated muscle metabolites were measured.
The combination of hypercarnitinemia (600 micromol/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.
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.
肉碱在骨骼肌中脂肪与碳水化合物氧化的整合过程中发挥着至关重要的作用，而在肥胖症和2型糖尿病中这一过程会受到损害。
本研究旨在探究骨骼肌总肉碱（TC）含量增加对肌肉燃料代谢的影响。
在两次随机访视期间，当血清胰岛素维持在生理高浓度时，静脉输注生理盐水（对照组）或左旋肉碱5小时。
7名健康、非素食的年轻男性（体重指数，26.1±1.6kg/m²）参与了诺丁汉大学的本研究。
测量骨骼肌丙酮酸脱氢酶复合体（PDC）活性及相关肌肉代谢物。
高肉碱血症（600微摩尔/升）和高胰岛素血症（160毫国际单位/升）共同作用使肌肉TC含量增加了15%（P<0.01），同时丙酮酸脱氢酶复合体活性降低了30%（P<0.05），肌肉乳酸含量降低了40%（P<0.05），与对照组相比，肌肉糖原含量在一夜之间增加了30%（P<0.01），长链酰基辅酶A含量增加了40%（P<0.05）。
这些结果表明，在高碳水化合物供应情况下，人体骨骼肌TC含量的急性增加会导致碳水化合物氧化受到抑制，这可能是由于肉碱介导的脂肪氧化增加所致。这些新发现可能对我们理解肌肉脂肪氧化的调节具有重要意义，特别是在运动期间，此时肉碱的可利用性可能会限制脂肪氧化，以及在已知肉碱代谢受损的肥胖症和2型糖尿病中。
