Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice.
Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice.
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DOI：
10.1371/journal.pone.0017090
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发表时间：
2011-02-24
期刊：
影响因子：
3.7
通讯作者：
Welle S
中科院分区：
文献类型：
--
作者：
Burgess K;Xu T;Brown R;Han B;Welle S
在结构性肌肉抑制素缺乏的小鼠中，明显的肌肉肥大减少了高脂肪喂养引起的脂肪堆积和高血糖，但尚不清楚由于发育后肌肉生长抑素活性丧失而导致的肌肉质量较小的增加是否在高脂肪喂养期间具有有益的代谢效应。因此，我们研究了发育后肌肉生长抑制素基因敲除对高脂饮食效果的影响。雄性小鼠普遍表达他莫昔芬诱导的Cre重组酶，在4月龄时给予他莫昔芬2周。这会耗尽携带myostatin基因的小鼠的myostatin，而不是携带正常myostatin基因的对照组小鼠。一些小鼠在停止喂食他莫昔芬2周后开始喂食高脂饮食(能量的60%)22周。肌肉生长抑制素耗竭使骨骼肌质量∼增加30%。在高脂肪喂养的前8周，肌肉发达的小鼠体重增加的∼比对照组小50%。在随后的3个月的高脂肪喂养中，对照组和肌肉生长抑素缺陷小鼠的额外体重增加相似。在高脂饮食5个月后，对照组和肌肉生长抑制素缺乏的小鼠的附睾垫和腹膜后脂肪垫的质量相似，尽管肌肉生长抑素缺乏减少了高脂饮食导致的体重增加(高脂饮食的平均体重减去低脂饮食的平均体重：对照组为19.9g，肌肉生长抑素缺乏的小鼠为14.1g)。在高脂喂养3个月或5个月后，消耗肌肉抑制素并没有改变空腹血糖水平，但在腹腔注射葡萄糖后90分钟测得的血糖水平有所下降。肌肉抑制素的缺乏还可以减轻肝脏脂肪变性和肌肉组织中的脂肪积聚。我们的结论是，在成熟后阻断肌肉生长抑制素信号可以减轻高脂饮食的一些不利影响。
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.
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影响因子：
4.1
作者：
Hittel DS;Axelson M;Sarna N;Shearer J;Huffman KM;Kraus WE
通讯作者：
Kraus WE
影响因子：
29
作者：
Izumiya, Yasuhiro;Hopkins, Teresa;Walsh, Kenneth
通讯作者：
Walsh, Kenneth
DOI：
10.1152/ajpendo.00433.2005
发表时间：
2006-03-01
影响因子：
5.1
作者：
Welle, S;Bhatt, K;Pinkert, CA
通讯作者：
Pinkert, CA
影响因子：
3.3
作者：
Personius, Kirkwood E.;Jayaram, Aditi;Welle, Stephen
通讯作者：
Welle, Stephen
DOI：
10.1006/bbrc.2002.6500
发表时间：
2002-03-01
影响因子：
3.1
作者：
Lin, J;Arnold, HB;Baile, CA
通讯作者：
Baile, CA