Schnuck Jamie K, Johnson Michele A, Gould Lacey M, Gannon Nicholas P, Vaughan Roger A
Department of Exercise Science, High Point University, One University Parkway, High Point, NC, 27268, USA.
School of Medicine, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Lipids. 2016 Oct;51(10):1127-1136. doi: 10.1007/s11745-016-4193-2. Epub 2016 Sep 6.
Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine-derived metabolite β-hydroxy-β-methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB-treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator-activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP-activated protein kinase. As a result, HMB-treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.
亮氨酸可调节肌肉中的合成和降解途径，这可能为运动员和患病群体带来代谢益处。亮氨酸在运动员中已很受欢迎，因为它能改善运动表现和身体成分，然而，人们对常见的亮氨酸衍生代谢物β-羟基-β-甲基丁酸酯（HMB）的代谢作用知之甚少。我们的研究测定了HMB对代谢蛋白表达、线粒体含量和代谢以及骨骼肌细胞中脂质含量的影响。具体而言，将培养的C2C12肌管分别用对照物或浓度范围为6.25至25μM的HMB处理24小时，然后测定mRNA和/或蛋白表达、耗氧量、葡萄糖摄取量和脂质含量。与亮氨酸对代谢的刺激作用相反，经HMB处理的细胞显示脂质氧化调节因子显著减少，包括过氧化物酶体增殖物激活受体α（PPARα）和PPARβ/δ，以及下游靶点肉碱棕榈酰转移酶，而葡萄糖或棕榈酸氧化没有改变。此外，HMB显著抑制了能量代谢主要调节因子AMP激活的蛋白激酶的激活。结果，与真正的对照或用亮氨酸处理效果不明确的细胞相比，经HMB处理的细胞的线粒体总含量也降低了。此外，与对照细胞相比，HMB处理增强了脂质生物合成标记物（PPARγ和脂肪酸合酶），并持续促进总脂质含量升高。总的来说，我们的结果表明，HMB并没有改善线粒体代谢或含量，并且可能通过提高PPARγ表达来促进细胞脂质含量升高。这些观察结果表明HMB可能对那些希望刺激细胞合成代谢过程的人群最为有益。
