Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice
Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice
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DOI：
10.1016/j.cmet.2007.11.003
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发表时间：
2008-02-01
期刊：
影响因子：
29
通讯作者：
Walsh, Kenneth
中科院分区：
文献类型：
--
作者：
Izumiya, Yasuhiro;Hopkins, Teresa;Walsh, Kenneth
与氧化肌肉纤维在调节全身新陈代谢中的作用形成鲜明对比的是，人们对快速/糖酵解肌肉纤维在这些过程中的作用知之甚少。在这里，我们产生了一种骨骼肌特异的、有条件的转基因小鼠，表达了一种结构性的活性形式的Akt1。转基因激活导致肌肉肥大，这是由于IIb型肌肉纤维的生长，并伴随着力量的增加。在饮食诱导的肥胖小鼠中，AKT1转基因诱导导致体重和脂肪质量的减少，肝脏脂肪变性的缓解，并改善代谢参数。AKT1介导的骨骼肌生长与高脂肪/高蔗糖饮食对肝脏转录表达模式的影响相反，并增加了肝脏脂肪酸氧化和酮体产生。我们的发现表明，快速/糖酵解肌肉质量的增加可以通过改变远端组织中的脂肪酸氧化来导致肥胖的消退和代谢的改善。
In contrast to the well-established role of oxidative muscle fibers in regulating whole-body metabolism, little is known about the function of fast/glycolytic muscle fibers in these processes. Here, we generated a skeletal muscle-specific, conditional transgenic mouse expressing a constitutively active form of Akt1. Transgene activation led to muscle hypertrophy due to the growth of type IIb muscle fibers, which was accompanied by an increase in strength. Akt1 transgene induction in diet-induced obese mice led to reductions in body weight and fat mass, resolution of hepatic steatosis, and improved metabolic parameters. Akt1-mediated skeletal muscle growth opposed the effects of a high-fat/high-sucrose diet on transcript expression patterns in the liver and increased hepatic fatty acid oxidation and ketone body production. Our findings indicate that an increase in fast/glycolytic muscle mass can result in the regression of obesity and metabolic improvement through its ability to alter fatty acid oxidation in remote tissues.