Jeanplong F, Osepchook C C, Falconer S J, Smith H K, Bass J J, McMahon C D, Oldham J M
AgResearch Ltd, Ruakura Research Centre, Hamilton 3240, New Zealand.
AgResearch Ltd, Ruakura Research Centre, Hamilton 3240, New Zealand; Department of Sport and Exercise Science, University of Auckland, Auckland, New Zealand.
Domest Anim Endocrinol. 2015 Jul;52:17-24. doi: 10.1016/j.domaniend.2015.01.002. Epub 2015 Jan 19.
Undernutrition suppresses the growth of skeletal muscles and alters the expression of insulin-like growth factor 1 (IGF1), a key mitogen, and myostatin, a potent inhibitor of myogenesis. These changes can explain, at least in part, the reduced growth of skeletal muscles in underfed lambs. We have recently identified a myostatin splice variant (MSV) that binds to and antagonizes the canonical signaling of myostatin. In the present study, we hypothesized that the expression of MSV would be reduced in conjunction with myostatin and IGF1 in response to underfeeding in skeletal muscles of sheep. Young growing ewes were fed either ad libitum or an energy-restricted diet (30% of maintenance requirements) for 28 d. This regime of underfeeding resulted in a 24% reduction in body mass (P < 0.001) and a 36% reduction in the mass of the semitendinosus muscles relative to controls (P < 0.001) by day 28. The concentrations of MSV and IGF1 messenger RNA (mRNA) were reduced (both P < 0.001), but myostatin mRNA was not altered in semitendinosus muscles. Unlike the reduced expression of mRNA, the abundance of MSV protein was increased (P < 0.05) and there was no change in the abundance of myostatin protein. Our results suggest that undernutrition for 28 d decreases the signaling of myostatin by increasing the abundance of MSV protein. Although this action may reduce the growth inhibitory activity of myostatin, it cannot prevent the loss of growth of skeletal muscles during undernutrition.
营养不良会抑制骨骼肌生长，并改变关键促有丝分裂原胰岛素样生长因子1（IGF1）以及肌肉生长抑制素（一种肌肉生成的强效抑制剂）的表达。这些变化至少可以部分解释饥饿羔羊骨骼肌生长减缓的现象。我们最近鉴定出一种肌肉生长抑制素剪接变体（MSV），它能结合并拮抗肌肉生长抑制素的经典信号传导。在本研究中，我们假设在绵羊骨骼肌中，MSV的表达会因饥饿而与肌肉生长抑制素和IGF1一起降低。将幼年生长母羊随意喂食或给予能量限制饮食（维持需求量的30%），持续28天。到第28天，这种饥饿方案导致体重降低24%（P<0.001），半腱肌质量相对于对照组降低36%（P<0.001）。半腱肌中MSV和IGF1信使核糖核酸（mRNA）的浓度降低（均为P<0.001），但肌肉生长抑制素mRNA未发生改变。与mRNA表达降低不同，MSV蛋白的丰度增加（P<0.05），而肌肉生长抑制素蛋白的丰度没有变化。我们的结果表明，28天的营养不良通过增加MSV蛋白的丰度降低了肌肉生长抑制素的信号传导。尽管这种作用可能会降低肌肉生长抑制素的生长抑制活性，但它无法防止营养不良期间骨骼肌生长的丧失。
