Laboratory of Muscle Biology and Sarcopenia, Division of Exercise Physiology,West Virginia University School of Medicine, Morgantown, WV 26506, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R701-15. doi: 10.1152/ajpregu.00840.2010. Epub 2011 Jun 22.
β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite shown to reduce protein catabolism in disease states and promote skeletal muscle hypertrophy in response to loading exercise. In this study, we evaluated the efficacy of HMB to reduce muscle wasting and promote muscle recovery following disuse in aged animals. Fisher 344×Brown Norway rats, 34 mo of age, were randomly assigned to receive either Ca-HMB (340 mg/kg body wt) or the water vehicle by gavage (n = 32/group). The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group). Nonsuspended control animals were compared with suspended animals after 14 days of HS (n = 8) or after R (n = 8). HMB treatment prevented the decline in maximal in vivo isometric force output after 2 wk of recovery from hindlimb unloading. The HMB-treated animals had significantly greater plantaris and soleus fiber cross-sectional area compared with the vehicle-treated animals. HMB decreased the amount of TUNEL-positive nuclei in reloaded plantaris muscles (5.1% vs. 1.6%, P < 0.05) and soleus muscles (3.9% vs. 1.8%, P < 0.05). Although HMB did not significantly alter Bcl-2 protein abundance compared with vehicle treatment, HMB decreased Bax protein abundance following R, by 40% and 14% (P < 0.05) in plantaris and soleus muscles, respectively. Cleaved caspase-3 was reduced by 12% and 9% (P < 0.05) in HMB-treated reloaded plantaris and soleus muscles, compared with vehicle-treated animals. HMB reduced cleaved caspase-9 by 14% and 30% (P < 0.05) in reloaded plantaris and soleus muscles, respectively, compared with vehicle-treated animals. Although, HMB was unable to prevent unloading-induced atrophy, it attenuated the decrease in fiber area in fast and slow muscles after HS and R. HMB's ability to protect against muscle loss may be due in part to putative inhibition of myonuclear apoptosis via regulation of mitochondrial-associated caspase signaling.
β-羟-β-甲基丁酸（HMB）是一种亮氨酸代谢物，已被证明可减少疾病状态下的蛋白质分解，并促进对加载运动的骨骼肌肥大。在这项研究中，我们评估了 HMB 减少老年动物失用后肌肉浪费和促进肌肉恢复的功效。34 月龄的 Fisher 344×Brown Norway 大鼠随机分为接受 Ca-HMB（340mg/kg 体重）或水载体灌胃（每组 32 只）。动物接受 14 天的后肢悬挂（HS，每组 8 只/饮食组）或 14 天的去负荷后再负荷（R；每组 8 只/饮食组）。未悬挂的对照动物与 14 天 HS 后的悬挂动物（n=8）或 R 后的悬挂动物（n=8）进行比较。HMB 治疗可防止后肢去负荷后 2 周恢复期间最大体内等长力输出的下降。与载体处理的动物相比，HMB 处理的动物的比目鱼肌和跖肌纤维横截面积明显更大。HMB 减少了再负荷的比目鱼肌（5.1%对 1.6%，P<0.05）和跖肌（3.9%对 1.8%，P<0.05）中 TUNEL 阳性核的数量。尽管与载体处理相比，HMB 对 Bcl-2 蛋白丰度没有显著影响，但 HMB 减少了 R 后 Bax 蛋白的丰度，分别减少了比目鱼肌和跖肌的 40%和 14%（P<0.05）。与载体处理的动物相比，再负荷的比目鱼肌和跖肌中的 cleaved caspase-3 减少了 12%和 9%（P<0.05）。与载体处理的动物相比，HMB 减少了再负荷的比目鱼肌和跖肌中的 cleaved caspase-9 分别减少了 14%和 30%（P<0.05）。虽然 HMB 不能防止去负荷引起的萎缩，但它减轻了 HS 和 R 后快肌和慢肌纤维面积的减少。HMB 防止肌肉损失的能力可能部分归因于通过调节与线粒体相关的 caspase 信号来抑制肌核凋亡。
