Department of Kinesiology, Michigan State University, East Lansing, MI.
Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY.
Med Sci Sports Exerc. 2023 Dec 1;55(12):2160-2169. doi: 10.1249/MSS.0000000000003259. Epub 2023 Jul 27.
Growth restriction (GR) reduces ribosome abundance and skeletal muscle mass in mice. A reduction in skeletal muscle mass increases the risk of frailty and is associated with high morbidity and mortality rates. As eccentric type exercise increases muscle mass, this investigation aimed to determine if eccentric loading of skeletal muscle via downhill running (DHR) increased muscle mass in GR mice.
Mice were growth-restricted either gestational undernutrition (GUN, n = 8 litters), postnatal undernutrition (PUN, n = 8 litters), or were not restricted (CON, n = 8 litters) via a validated cross-fostering nutritive model. On postnatal day (PN) 21, all mice were weaned to a healthy diet, isolating the period of GR to early life as seen in humans. At PN45, mice were assigned to either a DHR (CON, n = 4 litters; GUN, n = 4 litters; PUN, n = 4 litters) or sedentary (SED: CON, n = 4 litters; GUN, n = 4 litters; PUN, n = 4 litters) group. Downhill running (16% decline: 18 m·min -1 ) was performed in 30-min bouts, three times per week, for 12 wk on a rodent treadmill. At PN129, the quadriceps femoris was dissected and evaluated for mass, myofiber size and type, and molecular markers of growth.
Following training, CON-DHR mice having larger cells than CON-SED, GUN-SED, PUN-SED, and PUN-DHR mice ( P < 0.05). The PUN group (as compared with CON) had reduced body mass ( P < 0.001), upstream binding factor abundance ( P = 0.012), phosphor-mTOR ( P < 0.001), and quadriceps mass ( P = 0.02). The GUN and PUN groups had increased MuRF1 abundance ( P < 0.001) compared with CON ( P < 0.001).
The blunted response to training suggests GR mice may have anabolic resistance when exposed to eccentric type exercise.
生长受限（GR）会减少小鼠核糖体的数量和骨骼肌的质量。骨骼肌质量的减少会增加虚弱的风险，并与高发病率和死亡率相关。由于离心型运动可以增加肌肉质量，因此本研究旨在确定通过下坡跑步（DHR）对骨骼肌进行离心负荷是否会增加 GR 小鼠的肌肉质量。
通过经过验证的交叉寄养营养模型，对小鼠进行妊娠期营养不良（GUN，n = 8 窝）、产后营养不良（PUN，n = 8 窝）或不受限制（CON，n = 8 窝）的生长受限处理。在出生后第 21 天（PN），所有小鼠均断奶至健康饮食，将 GR 期隔离到人类早期生命阶段。在 PN45 时，将小鼠分配到 DHR（CON，n = 4 窝；GUN，n = 4 窝；PUN，n = 4 窝）或安静（SED：CON，n = 4 窝；GUN，n = 4 窝；PUN，n = 4 窝）组。下坡跑步（16%坡度下降：18 m·min -1 ）在啮齿动物跑步机上以 30 分钟为一组，每周 3 次，进行 12 周。在 PN129 时，解剖并评估股四头肌的质量、肌纤维大小和类型以及生长的分子标志物。
经过训练，CON-DHR 小鼠的细胞比 CON-SED、GUN-SED、PUN-SED 和 PUN-DHR 小鼠的细胞更大（P < 0.05）。与 CON 相比，PUN 组（与 CON 相比）体重（P < 0.001）、上游结合因子丰度（P = 0.012）、磷酸化-mTOR（P < 0.001）和股四头肌质量（P = 0.02）降低。GUN 和 PUN 组的 MuRF1 丰度（P < 0.001）均高于 CON（P < 0.001）。
训练反应迟钝表明，GR 小鼠在接受离心型运动时可能存在合成代谢抵抗。
