Guangdong Provincial Key Laboratory of Animal Nutrition Regulation, South China Agricultural University, Guangzhou, Guangdong, China.
Science College of Jiangxi Agricultural University, Nanchang, Jiangxi 330045, China.
Nutrition. 2019 Apr;60:217-226. doi: 10.1016/j.nut.2018.09.032. Epub 2018 Oct 23.
Mitochondrial dysfunction in skeletal muscle has emerged as key to the development of obesity and its related metabolic disorders. Leucine (Leu) is an essential amino acid that has been reported to increase mitochondrial biogenesis in muscle cells, as has its metabolite β-hydroxy-β-methylbutyrate (HMB). However, two questions-which one is more potent and what is the cellular mechanisms of the action of Leu and HMB-remain to be answered. Therefore we aimed to investigate the effects of Leu and HMB on mitochondrial function in C2 C12 myotubes and analyze the underlying molecular mechanism.
The effects of Leu and HMB on mitochondrial mass, mitochondrial respiration capacity, and the expression of genes related to mitochondrial biogenesis were evaluated in C2 C12 myotubes. Differentiated myotubes were treated with Leu (0.5 mM) or HMB (50 μM) with or without PPARβ/δ antagonist (GSK3787, 1 μM) and CDK4 antagonist (LY2835219, 1.5 μM), respectively, for 24 h. The results indicated that treatment with Leu or HMB significantly increased mitochondrial mass, mitochondrial respiration capacity, and the messenger RNA expression of genes associated with mitochondrial biogenesis (P < 0.05). In addition, these positive effects of Leu or HMB on these parameters were attenuated by GSK3787 and LY2835219 treatments (P < 0.05).
Our results provide evidence indicating that as with Leu, HMB alone could increase mitochondrial biogenesis and function via regulation of PPARβ/δ and CDK4 pathways. Moreover, HMB seems to be more potent than Leu in the positive regulation of mitochondrial biogenesis and function in C2 C12 myotubes because the dosage used for HMB was much lower than that for Leu.
骨骼肌中的线粒体功能障碍已成为肥胖及其相关代谢紊乱发展的关键。亮氨酸（Leu）是一种必需氨基酸，据报道它能增加肌肉细胞中的线粒体生物发生，其代谢物β-羟基-β-甲基丁酸（HMB）也是如此。然而，有两个问题——哪一个更有效，以及 Leu 和 HMB 的作用机制是什么——仍有待回答。因此，我们旨在研究 Leu 和 HMB 对 C2 C12 肌管中线粒体功能的影响，并分析潜在的分子机制。
在 C2 C12 肌管中评估了 Leu 和 HMB 对线粒体质量、线粒体呼吸能力以及与线粒体生物发生相关的基因表达的影响。分化的肌管分别用 Leu（0.5 mM）或 HMB（50 μM）处理，并用或不用过氧化物酶体增殖物激活受体β/δ拮抗剂（GSK3787，1 μM）和细胞周期蛋白依赖性激酶 4 拮抗剂（LY2835219，1.5 μM）处理 24 小时。结果表明，用 Leu 或 HMB 处理可显著增加线粒体质量、线粒体呼吸能力以及与线粒体生物发生相关的基因的信使 RNA 表达（P < 0.05）。此外，GSK3787 和 LY2835219 处理减弱了 Leu 或 HMB 对这些参数的这些积极影响（P < 0.05）。
我们的结果提供了证据，表明与 Leu 一样，HMB 单独通过调节过氧化物酶体增殖物激活受体β/δ和细胞周期蛋白依赖性激酶 4 途径就能增加线粒体生物发生和功能。此外，由于 HMB 的用量远低于 Leu，因此 HMB 似乎比 Leu 更能积极调节 C2 C12 肌管中的线粒体生物发生和功能。
