Elevated circulating branched-chain amino acids (BCAA) such as leucine have been consistently correlated with increasing severity of insulin resistance across numerous populations. BCAA may promote insulin resistance through either mTOR-mediated suppression of insulin receptor substrate-1 or through the accumulation of toxic BCAA catabolites. Although the link between circulating BCAA and insulin resistance has been consistent, it has yet to be concluded if BCAA causally contribute to the development or worsening of insulin resistance. This work investigated the effect of leucine both with and without varying levels of insulin resistance on metabolism, metabolic gene expression, and insulin signaling. C2C12 myotubes were treated with and without varied concentrations of leucine up to 2 mM for 24 h both with and without varied levels of insulin resistance. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Mitochondrial metabolism was measured via O2 consumption. Leucine at 2 mM increased oxidative metabolism as well as gene expression of mitochondrial biogenesis, which was associated with increased cellular lipid content. Despite increased lipid content of leucine-treated cells, neither acute nor chronic leucine treatment at 2 mM affected insulin signaling in insulin sensitive, mildly insulin resistant, or severely insulin resistant cells. Similarly, leucine at lower concentrations (0.25 mM, 0.5 mM, and 1 mM) did not alter insulin signaling either, regardless of insulin resistance. Leucine appears to improve myotube oxidative metabolism and related metabolic gene expression. And despite increased lipid content of leucine-treated cells, leucine does not appear to alter insulin sensitivity either acutely or chronically, regardless of level of insulin resistance.

中文翻译：

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亮氨酸可增加线粒体代谢和脂质含量，而不会改变肌管中的胰岛素信号传导。

升高的循环支链氨基酸（BCAA）（如亮氨酸）一直与众多人群中胰岛素抵抗的严重程度不断增加相关。BCAA可能通过mTOR介导的胰岛素受体底物1抑制或通过有毒BCAA分解代谢产物的积累来促进胰岛素抵抗。尽管循环中的BCAA与胰岛素抵抗之间的联系一直是一致的，但尚无定论BCAA是否因果促进胰岛素抵抗的发展或恶化。这项工作研究了亮氨酸在有和没有不同水平的胰岛素抵抗下对代谢，代谢基因表达和胰岛素信号传导的影响。在有和无胰岛素抵抗水平的情况下，用和不使用浓度高达2 mM的亮氨酸处理C2C12肌管24小时。基因和蛋白质表达分别通过qRT-PCR和Western blot检测。通过消耗氧气来测量线粒体的新陈代谢。2 mM的亮氨酸增加氧化代谢以及线粒体生物发生的基因表达，这与细胞脂质含量增加有关。尽管亮氨酸处理细胞的脂质含量增加，但是在2 mM的急性和慢性亮氨酸处理都不会影响胰岛素敏感，轻度胰岛素抵抗或严重胰岛素抵抗细胞中的胰岛素信号传导。同样，无论胰岛素抵抗如何，较低浓度（0.25 mM，0.5 mM和1 mM）的亮氨酸也不会改变胰岛素信号。亮氨酸似乎可以改善肌管的氧化代谢和相关的代谢基因表达。尽管亮氨酸处理过的细胞脂质含量增加，但无论胰岛素抵抗水平如何，亮氨酸都不会急性或慢性改变胰岛素敏感性。