Department of Exercise Science, High Point University, High Point, NC, USA.
Department of Exercise Science, High Point University, High Point, NC, USA.
Biochimie. 2020 Jan;168:124-133. doi: 10.1016/j.biochi.2019.10.017. Epub 2019 Nov 2.
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 O 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.
循环支链氨基酸（BCAA）水平升高，如亮氨酸，与多种人群的胰岛素抵抗严重程度增加呈正相关。BCAA 可能通过 mTOR 介导的胰岛素受体底物-1抑制或通过有毒的 BCAA 代谢产物的积累来促进胰岛素抵抗。虽然循环 BCAA 与胰岛素抵抗之间的联系是一致的，但尚未确定 BCAA 是否会导致胰岛素抵抗的发展或恶化。本研究调查了亮氨酸在存在或不存在不同程度胰岛素抵抗的情况下对代谢、代谢基因表达和胰岛素信号的影响。用不同浓度的亮氨酸（高达 2mM）处理 C2C12 肌管 24 小时，无论是否存在不同程度的胰岛素抵抗，均用或不用亮氨酸处理。通过 qRT-PCR 和 Western blot 分别测量基因和蛋白质表达。通过 O 消耗测量线粒体代谢。2mM 的亮氨酸增加了氧化代谢以及线粒体生物发生的基因表达，这与细胞脂质含量的增加有关。尽管亮氨酸处理的细胞脂质含量增加，但在胰岛素敏感、轻度胰岛素抵抗和重度胰岛素抵抗的细胞中，急性或慢性 2mM 亮氨酸处理均不影响胰岛素信号。同样，在较低浓度（0.25mM、0.5mM 和 1mM）的亮氨酸也不改变胰岛素信号，无论胰岛素抵抗如何。亮氨酸似乎改善了肌管的氧化代谢和相关的代谢基因表达。尽管亮氨酸处理的细胞脂质含量增加，但亮氨酸无论是急性还是慢性，都不会改变胰岛素敏感性，无论胰岛素抵抗的程度如何。
