Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation.
Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation.
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DOI：
10.1371/journal.pone.0120524
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Patel K
中科院分区：
文献类型：
--
作者：
Collins-Hooper H;Sartori R;Giallourou N;Matsakas A;Mitchell R;Makarenkova HP;Flasskamp H;Macharia R;Ray S;Swann JR;Sandri M;Patel K
动物充满了从组织/器官到细胞尺度的适应机制，这些机制确保了在大小变化的情况下保持动态平衡的过程。然而，我们和其他人已经假设，适应的程度是有限的，一旦超出正常水平的大小波动，细胞和组织的功能异常的方式。在这项研究中，我们研究了肌肉生长抑制素基因敲除小鼠的肌肉功能，这是一个很好的模型，用于研究超出正常生长水平的肥大和急性饥饿恢复质量的后果。我们发现肌肉生长是通过血清/糖皮质激素激酶1（SGK 1）而不是Akt 1驱动的蛋白质合成来维持的。此外，我们对肥大肌肉的代谢组学分析表明，来自营养源的碳被引导用于生物质的生产，而不是ATP的生产。然而，肌肉显示出自噬水平升高和肌肉张力水平降低。我们证明了肌肉生长抑制素无效肌肉对饮食变化非常敏感，并激活蛋白水解和自噬程序，并比野生型更广泛地关闭蛋白质合成。令人痛心的是，我们表明，急性饥饿，这是有害的野生型动物是有益的代谢和肌肉功能的肌肉生长抑制素基因敲除小鼠通过正常化的紧张生产。
Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
29
作者：
Lokireddy, Sudarsanareddy;Wijesoma, Isuru W.;Kambadur, Ravi
通讯作者：
Kambadur, Ravi
影响因子：
82.9
作者：
Grumati, Paolo;Coletto, Luisa;Bonaldo, Paolo
通讯作者：
Bonaldo, Paolo
DOI：
10.1073/pnas.85.9.3175
发表时间：
1988-05-01
影响因子：
11.1
作者：
KOHEN, R;YAMAMOTO, Y;AMES, BN
通讯作者：
AMES, BN
影响因子：
3.5
作者：
Kurapati, Ramakrishna;McKenna, Caoimhe;Blanco, Gonzalo
通讯作者：
Blanco, Gonzalo