Power R A, Hulver M W, Zhang J Y, Dubois J, Marchand R M, Ilkayeva O, Muoio D M, Mynatt R L
Division of Nutrition and Chronic Disease, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Diabetologia. 2007 Apr;50(4):824-32. doi: 10.1007/s00125-007-0605-4. Epub 2007 Feb 20.
AIMS/HYPOTHESIS: This study examined the efficacy of supplemental L: -carnitine as an adjunctive diabetes therapy in mouse models of metabolic disease. We hypothesised that carnitine would facilitate fatty acid export from tissues in the form of acyl-carnitines, thereby alleviating lipid-induced insulin resistance.
Obese mice with genetic or diet-induced forms of insulin resistance were fed rodent chow +/- 0.5% L: -carnitine for a period of 1-8 weeks. Metabolic outcomes included insulin tolerance tests, indirect calorimetry and mass spectrometry-based profiling of acyl-carnitine esters in tissues and plasma.
Carnitine supplementation improved insulin-stimulated glucose disposal in genetically diabetic mice and wild-type mice fed a high-fat diet, without altering body weight or food intake. In severely diabetic mice, carnitine supplementation increased average daily respiratory exchange ratio from 0.886 +/- 0.01 to 0.914 +/- 0.01 (p < 0.01), reflecting a marked increase in systemic carbohydrate oxidation. Similarly, under insulin-stimulated conditions, carbohydrate oxidation was higher and total energy expenditure increased from 172 +/- 10 to 210 +/- 9 kJ kg fat-free mass(-1) h(-1) in the carnitine-supplemented compared with control animals. These metabolic improvements corresponded with a 2.3-fold rise in circulating levels of acetyl-carnitine, which accounts for 86 and 88% of the total acyl-carnitine pool in plasma and skeletal muscle, respectively. Carnitine supplementation also increased several medium- and long-chain acyl-carnitine species in both plasma and tissues.
CONCLUSIONS/INTERPRETATION: These findings suggest that carnitine supplementation relieves lipid overload and glucose intolerance in obese rodents by enhancing mitochondrial efflux of excess acyl groups from insulin-responsive tissues. Carefully controlled clinical trials should be considered.
目的/假设：本研究在代谢性疾病小鼠模型中检验了补充左旋肉碱作为糖尿病辅助治疗的疗效。我们假设肉碱将促进脂肪酸以酰基肉碱的形式从组织中输出，从而减轻脂质诱导的胰岛素抵抗。
对具有遗传或饮食诱导形式胰岛素抵抗的肥胖小鼠喂食含或不含0.5%左旋肉碱的啮齿动物饲料，持续1至8周。代谢结果包括胰岛素耐量试验、间接量热法以及基于质谱的组织和血浆中酰基肉碱酯的谱分析。
补充肉碱改善了遗传性糖尿病小鼠和喂食高脂饮食的野生型小鼠中胰岛素刺激的葡萄糖处置，而不改变体重或食物摄入量。在重度糖尿病小鼠中，补充肉碱使平均每日呼吸交换率从0.886±0.01提高到0.914±0.01（p<0.01）。反映全身碳水化合物氧化显著增加。同样，在胰岛素刺激条件下，与对照动物相比，补充肉碱的动物碳水化合物氧化更高，总能量消耗从172±10增加到210±9kJ·kg去脂体重-1·h-1。这些代谢改善与循环中乙酰肉碱水平升高2.3倍相对应，乙酰肉碱分别占血浆和骨骼肌中总酰基肉碱池的86%和88%。补充肉碱还增加了血浆和组织中几种中链和长链酰基肉碱种类。
结论/解读：这些发现表明，补充肉碱通过增强胰岛素反应性组织中过量酰基的线粒体流出，减轻肥胖啮齿动物的脂质过载和葡萄糖不耐受。应考虑进行严格控制的临床试验。
