Endocrinology and Metabolism Division, Department of Medicine, University of Rochester, Rochester, New York, United States of America.
PLoS One. 2011 Feb 24;6(2):e17090. doi: 10.1371/journal.pone.0017090.
The marked hypermuscularity in mice with constitutive myostatin deficiency reduces fat accumulation and hyperglycemia induced by high-fat feeding, but it is unclear whether the smaller increase in muscle mass caused by postdevelopmental loss of myostatin activity has beneficial metabolic effects during high-fat feeding. We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding. Male mice with ubiquitous expression of tamoxifen-inducible Cre recombinase were fed tamoxifen for 2 weeks at 4 months of age. This depleted myostatin in mice with floxed myostatin genes, but not in control mice with normal myostatin genes. Some mice were fed a high-fat diet (60% of energy) for 22 weeks, starting 2 weeks after cessation of tamoxifen feeding. Myostatin depletion increased skeletal muscle mass ∼30%. Hypermuscular mice had ∼50% less weight gain than control mice over the first 8 weeks of high-fat feeding. During the subsequent 3 months of high-fat feeding, additional weight gain was similar in control and myostatin-deficient mice. After 5 months of high-fat feeding, the mass of epididymal and retroperitoneal fat pads was similar in control and myostatin-deficient mice even though myostatin depletion reduced the weight gain attributable to the high-fat diet (mean weight with high-fat diet minus mean weight with low-fat diet: 19.9 g in control mice, 14.1 g in myostatin-deficient mice). Myostatin depletion did not alter fasting blood glucose levels after 3 or 5 months of high-fat feeding, but reduced glucose levels measured 90 min after intraperitoneal glucose injection. Myostatin depletion also attenuated hepatic steatosis and accumulation of fat in muscle tissue. We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet.
肌肉生长抑制素缺失导致的肌肉明显过度生长可减少高脂肪喂养引起的脂肪堆积和高血糖，但尚不清楚肌肉生长抑制素活性的后天性丧失引起的肌肉质量较小增加在高脂肪喂养期间是否具有有益的代谢作用。因此，我们研究了后天性肌肉生长抑制素敲除如何影响高脂肪喂养的影响。雄性小鼠在 4 月龄时用他莫昔芬诱导的 Cre 重组酶进行全身性表达，用他莫昔芬喂养 2 周。这耗尽了 floxed 肌肉生长抑制素基因的小鼠中的肌肉生长抑制素，但没有耗尽正常肌肉生长抑制素基因的对照小鼠中的肌肉生长抑制素。一些小鼠在停止他莫昔芬喂养后 2 周开始用高脂肪饮食（能量的 60%）喂养 22 周。肌肉生长抑制素耗竭使骨骼肌质量增加约 30%。与对照组相比，高脂喂养的前 8 周，肌肉过度生长的小鼠体重增加减少了约 50%。在随后的 3 个月高脂喂养期间，对照组和肌肉生长抑制素缺乏小鼠的体重增加相似。高脂喂养 5 个月后，即使肌肉生长抑制素耗竭减少了高脂肪饮食引起的体重增加（高脂肪饮食的平均体重减去低脂饮食的平均体重：对照组为 19.9 克，肌肉生长抑制素缺乏组为 14.1 克），对照组和肌肉生长抑制素缺乏组的附睾和腹膜后脂肪垫的质量相似。肌肉生长抑制素耗竭并没有改变高脂肪喂养 3 或 5 个月后的空腹血糖水平，但降低了腹腔内葡萄糖注射后 90 分钟的血糖水平。肌肉生长抑制素耗竭还减轻了肝脂肪变性和肌肉组织脂肪堆积。我们的结论是，成熟后阻断肌肉生长抑制素信号可以减轻高脂肪饮食的一些不良影响。
