Leucine Supplementation Differently Modulates Branched-Chain Amino Acid Catabolism, Mitochondrial Function and Metabolic Profiles at the Different Stage of Insulin Resistance in Rats on High-Fat Diet.
Leucine Supplementation Differently Modulates Branched-Chain Amino Acid Catabolism, Mitochondrial Function and Metabolic Profiles at the Different Stage of Insulin Resistance in Rats on High-Fat Diet.
复制标题
补充亮氨酸不同地调节高脂饮食大鼠胰岛素抵抗不同阶段的支链氨基酸分解代谢、线粒体功能和代谢特征
DOI：
10.3390/nu9060565
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发表时间：
2017-06-02
期刊：
影响因子：
5.9
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Liu R;Li H;Fan W;Jin Q;Chao T;Wu Y;Huang J;Hao L;Yang X
关于支链氨基酸（BCAAs）——尤其是亮氨酸——与胰岛素抵抗之间的关系，现有的研究结果是相互矛盾的。根据分解代谢和合成代谢状态的不同，支链氨基酸被认为会产生不同甚至相反的作用。我们检验了补充亮氨酸可能在胰岛素抵抗的不同阶段发挥不同作用的假设，为亮氨酸在胰岛素抵抗进展中的作用提供机制见解。雄性Sprague-Dawley大鼠被喂食正常食物、高脂肪食物（HFD）、添加1.5%亮氨酸的高脂肪食物或卡路里限制20%的高脂肪食物，为期24或32周。在胰岛素抵抗的早期（24周），补充亮氨酸导致饲喂hfd的大鼠BCAA的异常分解代谢和脂质不完全氧化，导致骨骼肌线粒体功能障碍。然而，补充亮氨酸对BCAA分解代谢没有显著影响，但在高血糖期（32周），确实增强了线粒体生物发生，同时改善了脂质氧化和线粒体功能。这些发现表明，亮氨酸在胰岛素抵抗的不同阶段对代谢特征的影响不同，应该仔细考虑生物体的整体代谢状态，以增强亮氨酸的益处。
The available findings concerning the association between branched-chain amino acids (BCAAs)—particularly leucine—and insulin resistance are conflicting. BCAAs have been proposed to elicit different or even opposite effects, depending on the prevalence of catabolic and anabolic states. We tested the hypothesis that leucine supplementation may exert different effects at different stages of insulin resistance, to provide mechanistic insights into the role of leucine in the progression of insulin resistance. Male Sprague-Dawley rats were fed a normal chow diet, high-fat diet (HFD), HFD supplemented with 1.5% leucine, or HFD with a 20% calorie restriction for 24 or 32 weeks. Leucine supplementation led to abnormal catabolism of BCAA and the incompletely oxidized lipid species that contributed to mitochondrial dysfunction in skeletal muscle in HFD-fed rats in the early stage of insulin resistance (24 weeks). However, leucine supplementation induced no remarkable alternations in BCAA catabolism, but did enhance mitochondrial biogenesis with a concomitant improvement in lipid oxidation and mitochondrial function during the hyperglycaemia stage (32 weeks). These findings suggest that leucine trigger different effects on metabolic signatures at different stages of insulin resistance, and the overall metabolic status of the organisms should be carefully considered to potentiate the benefits of leucine.