生物谷报道：美国国立卫生研究院的科研人员近日研究发现，限制营养的供应可以阻碍肌肉干细胞发育为成熟的肌细胞。
一直以来，获取营养物质对于人体细胞的发育有着深远的影响是公认的道理，但是科学家尚不太清楚对其中的原因。此次，研究人员通过调查葡萄糖量研究如何影响肌肉干细胞分化为成熟的骨骼肌纤维。
研究人员发现，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。研究人员推测，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。
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。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。（生物谷www.bioon.com）
生物谷推荐原始出处：
Developmental Cell，Vol 14, 661-673，Marcella Fulco，Vittorio Sartorelli
Glucose Restriction Inhibits Skeletal Myoblast Differentiation by Activating SIRT1 through AMPK-Mediated Regulation of Nampt
Marcella Fulco,1 Yana Cen,2 Po Zhao,3 Eric P. Hoffman,3 Michael W. McBurney,4 Anthony A. Sauve,2 and Vittorio Sartorelli1,
1 Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA
2 Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
3 Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA
4 Ottawa Health Research Center Institute, 501 Smyth Road, Ottawa K1H 8L6, Canada
Summary
It is intuitive to speculate that nutrient availability may influence differentiation of mammalian cells. Nonetheless, a comprehensive complement of the molecular determinants involved in this process has not been elucidated yet. Here, we have investigated how nutrients (glucose) affect skeletal myogenesis. Glucose restriction (GR) impaired differentiation of skeletal myoblasts and was associated with activation of the AMP-activated protein kinase (AMPK). Activated AMPK was required to promote GR-induced transcription of the NAD+ biosynthetic enzyme Nampt. Indeed, GR augmented the Nampt activity, which consequently modified the intracellular [NAD+]:[NADH] ratio and nicotinamide levels, and mediated inhibition of skeletal myogenesis. Skeletal myoblasts derived from SIRT1+/− heterozygous mice were resistant to the effects of either GR or AMPK activation. These experiments reveal that AMPK, Nampt, and SIRT1 are the molecular components of a functional signaling pathway that allows skeletal muscle cells to sense and react to nutrient availability.
