vnewjay

Although it is certainly rational to expect that access to nutrients, such as the simple sugar glucose, has a profound impact on the development of human cells, the cellular strategies for responding to fluctuations in nutrient availability are not well understood. Drs. Vittorio Sartorelli and Marcella Fulco from the National Institutes of Health investigated how the availability of glucose affects the ability of muscle stem cells, called myoblasts, to develop (or "differentiate") into mature skeletal muscle fibers.

The researchers found that glucose restriction (GR) impaired differentiation of skeletal myoblasts and activated AMP-activated protein kinase (AMPK). These results define a pathway in which activation of AMPK in response to low glucose levels stimulates expression of the NAD+ biosynthetic enzyme Nampt. NAD+ is a known cofactor of SIRT1, which plays an important role in numerous physiological processes, including differentiation of skeletal muscle cells, and has been implicated in regulation of lifespan and aging. Importantly, inhibition of AMPK, Nampt or SIRT1 resulted in skeletal muscle cells that were oblivious to a nutrient poor environment and were able to differentiate under conditions that otherwise would not be suitable.

These results demonstrate that a defined pathway actively controls muscle differentiation in response to low nutrients. "We speculate that, functioning as a cellular checkpoint, the AMPK-Nampt-SIRT1 pathway may be activated by reduced nutrient availability to prevent cells from undertaking energy demanding processes -- such as cell differentiation -- during calorie-unfavorable conditions. On the other hand, once nutrients become available, the pathway is inactivated to allow resumption of physiological development," offers Dr. Sartorelli.

The study has important implications that extend beyond muscle development. This mechanism also operates in adult tissues and thus would be part of the response to a dietary regimen that restricts caloric intake. Further, the researchers found that glucose restriction or treatment of skeletal muscle cells with metformin, a drug used to treat type II diabetes, had similar outcomes and resulted in the activation of SIRT1. "It is therefore possible that the well-known benefits that diabetics derive from lowering the calorie intake in their diet may be attributable to activation of the AMPK-Nampt-SIRT1 axis" comments Dr. Sartorelli. It is also attractive to speculate that AMPK and SIRT1 may prove to be rational targets for counteracting the devastating effects of muscle wasting.

vnewjay

一项新的研究发现，限制营养的供应可以阻止肌肉干细胞发育到成熟的肌细胞。这项研究提供了关于正在发育的肌细胞如何感知和响应营养水平的令人兴奋的新信息。这项研究为正在进行的关于限制热量对生理和衰老的影响的研究提供了新的转折，而且可能导致治疗肌肉萎缩的新疗法。

尽管认为获取营养——诸如葡萄糖这种单糖——对于人体细胞的发育有着深远的影响是很合理的，但是科学家尚不太清楚对营养水平的涨落做出响应的细胞策略。美国国立卫生研究院的Vittorio Sartorelli博士和Marcella Fulco博士调查了葡萄糖的多少如何影响肌肉干细胞（称为成肌细胞）发育（或者称为“分化”）到成熟的骨骼肌纤维的能力。

这组科学家发现，葡萄糖限制（GR）会削弱骨骼肌成肌细胞的分化，而且会激活腺苷酸活化蛋白激酶（AMPK）。这些结果表明了一个路径，即对低葡萄糖水平做出响应的AMPK的活化会刺激NAD+合成酶Nampt的表达。已知NAD+是SIRT1 的一种辅助因子，后者在众多生理过程中扮演着一个重要的角色，包括骨骼肌细胞的分化，而且还牵扯到了寿命和衰老的调整。重要的是，抑制AMPK、Nampt或 SIRT1导致骨骼肌细胞不介意一个营养不良的环境，而且可以在一些本不适合的环境下分化。

这些结果表明了一个响应低营养环境、积极地控制肌肉分化的详细路径。“我们推测，AMPK-Nampt-SIRT1路径的作用就像一个细胞检查站，它可能被营养物质供应的减少而活化，从而阻止细胞在缺乏热量的条件下从事需要能量的过程——诸如细胞分化。另一方面，一旦营养物质供应恢复，这条路径就被关闭，从而让生理发育恢复，” Sartorelli博士提出。

这项研究的重要意义超出了细胞发育。这一机制还能在成体组织里运作，因此它可能成为对限制热量摄入的节食疗法的响应的一部分。此外，这组科学家还发现葡萄糖限制或者用二甲双胍（一种用于治疗II型糖尿病的药物）治疗骨骼肌细胞也有类似的结果，而且导致了SIRT1的活化。“因此，糖尿病患者从降低饮食的热量摄入中获得的众所周知的益处可能是由于AMPK-Nampt-SIRT1路径活化的贡献，” Sartorelli博士评论说。另外，一个具有吸引力的推测是，AMPK 和SIRT1可能被证明是用制止肌肉萎缩的破坏性效应的合理靶标。

dragon513

这是一个好信息，对于目前的研究有不少新的启示。从宏观上也更好理解营养的生理功能和意义了。谢谢LZ交流。LZ能谈谈你对这个的研究的看法吗？

vnewjay

能量对人类的影响具有非常广泛的意义！

但是，文章中所说的毕竟是在营养缺乏的条件下所出现的现象，那么这种现象也许只是机体代偿所产生的，不一定适用于正常生理条件下。

因此，所提出的观点有待在正常营养供给条件下验证！