Department of Clinical Medicine, Sapienza University of Rome, Italy.
Int J Oncol. 2011 Mar;38(3):713-20. doi: 10.3892/ijo.2010.885. Epub 2010 Dec 23.
β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMB-enriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2α, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2α markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2α levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.
β-羟基-β-甲基丁酸（HMB），一种亮氨酸代谢物，可改善肌肉质量和功能。本研究旨在评估 HMB 在癌症恶病质（CC）的实验体内模型中的给药效果。Wistar 大鼠随机分为接受标准或 4％HMB 强化饲料的组。两组大鼠均随机接受腹腔接种 AH-130 细胞（TB）。所有大鼠在第 24 天称重并处死。分离和称重肝脏，心脏和肌肉。通过 Western 印迹法在比目鱼肌（GSN）上评估 p-p70S6k，p-eIf2α，p-mTOR 和 p-4-EB-P1 的蛋白水平。如预期的那样，AH-130 腹水肝癌的生长导致明显的体重和 GSN 肌肉损失。HMB 治疗可显著增加对照组的 GSN 和心脏重量（p=0.002 和 p<0.001）。在 HMB 治疗的 TB 中，体重没有减轻，但显著增加（p=0.003），与 TB 相比，GSN 损失明显减轻（p=0.04）。与 C 相比，TB 大鼠的磷酸化 eIF2α显着降低。用 HMB 强化饮食喂养可导致对照动物的 p-eIF2α水平降低，而在 TB 组中未观察到变化。磷酸化 p70S6K 和磷酸化 mTOR 被 HMB 治疗在对照中显著增加，并且在 TB 中进一步增加。磷酸化 4-EB-P1 在 TB 中显着增加，但受 HMB 治疗的影响不大。HMB 的给药可减轻实验性 CC 中的体重和肌肉损失。关键合成代谢分子的磷酸化增加表明，这些作用是通过肌肉中蛋白质合成代谢的改善介导的。
