Chronic high fat feeding attenuates load-induced hypertrophy in mice
Chronic high fat feeding attenuates load-induced hypertrophy in mice
复制标题
DOI：
10.1113/jphysiol.2009.180174
复制
发表时间：
2009-12-01
影响因子：
5.5
通讯作者：
Rutledge, John C.
中科院分区：
文献类型：
--
作者：
Sitnick, Mitchell;Bodine, Sue C.;Rutledge, John C.
肥胖和肥胖相关疾病的发生率正在增加，如代谢综合征和胰岛素抵抗。肥胖对骨骼肌功能的影响，特别是对肌肉质量的调节，目前还知之甚少。在这项研究中，我们调查了饮食诱导的肥胖对骨骼肌对强加的生长刺激的反应能力的影响，例如增加的负荷。将雄性C57BL/6小鼠随机分为两组：低脂高碳水化合物饲料组(LFD)和高脂低碳水化合物饲料组(HFD)。每组小鼠分成两组：安静对照组和双侧足底肌功能超负荷(FO)组。分别于FO后3、7、14、30天对小鼠进行评估。经14天的FO，有10%的绝对增长减少(P<；0.05)对超负荷反应的HFD小鼠与LFD小鼠。到30天时，HFD小鼠的生长衰减比LFD小鼠增加了16%。在FO后，相对于LFD小鼠，HFD小鼠多聚体的形成减少，这表明蛋白质翻译减少。此外，与LFD小鼠相比，HFD小鼠对机械负荷增加的Akt和S6K1的激活显著减弱。综上所述，慢性高脂喂养会损害骨骼肌对机械负荷增加的反应能力。这一失败与激活Akt/mTOR信号通路的关键成员和增加蛋白质翻译的失败是一致的。
The incidence of obesity and obesity-related conditions, such as metabolic syndrome and insulin resistance, is on the increase. The effect of obesity on skeletal muscle function, especially the regulation of muscle mass, is poorly understood. In this study we investigated the effect of diet-induced obesity on the ability of skeletal muscle to respond to an imposed growth stimulus, such as increased load. Male C57BL/6 mice were randomized into two diet groups: a low fat, high carbohydrate diet (LFD) and a high fat, low carbohydrate diet (HFD) fed ad libitum for 14 weeks. Mice from each diet group were divided into two treatment groups: sedentary control or bilateral functional overload (FO) of the plantaris muscle. Mice were evaluated at 3, 7, 14 or 30 days following FO. By 14 days of FO, there was a 10% reduction (P < 0.05) in absolute growth of the plantaris in response to overload in HFD mice vs. LFD mice. By 30 days the attenuation in growth increased to 16% in HFD mice compared to LFD mice. Following FO, there was a reduction in the formation of polysomes in the HFD mice relative to the LFD mice, suggesting a decrease in protein translation. Further, activation of Akt and S6K1, in response to increased mechanical loading, was significantly attenuated in the HFD mice relative to the LFD mice. In conclusion, chronic high fat feeding impairs the ability of skeletal muscle to hypertrophy in response to increased mechanical load. This failure coincided with a failure to activate key members of the Akt/mTOR signalling pathway and increase protein translation.