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------来源：生物谷
本期杂志封面
在Cell Metabolism 9月份期刊上的一份研究报告中，科研人员给谚语“以食见人”（You are what you eat）赋予了一种新的意义。
研究人员从人类糖尿病患者的肌肉组织提取了DNA，这些糖尿病患者含有特定的化学标记。该表观遗传学标记可以在控制葡萄糖或脂肪数量的基因中发现。这些标记同样可以在糖尿病前期患者的骨骼肌中发现，表明DNA修饰可能是糖尿病发生的早期事件。
这些变化快速重编了基因的活性，而无需改变底层的DNA序列。研究人员解释说，环境因素，包括我们吃的食物，我们的活动都有可能影响到基因，这种改变可能更有利也可能更坏。
研究人员表示，当肌肉组织暴露于炎性环境或游离脂肪酸环境下时，基因PGC-1α就会发生过度甲基化。同样，当肌肉组织暴露在模拟的糖尿病环境下时，这种DNA改变也会发生。
据研究人员介绍，DNA改变是一个动态的过程。虽然糖尿病的遗传学原因很重要，但是表观特征的改变也能影响机体一些重要的生理学过程。研究表明，与饮食有关的因子可能会影响表观基因对糖尿病的控制。
这项研究表明，我们不是“基因的受害者”。如果身体的活动或其他的生活方式能够积极影响我们的基因组，改善新陈代谢，那么这或许为降低疾病风险提供了一种新的方法。
接下来，研究人员将关注是否不同的饮食和运动习惯会以有利于机体的方式改变DNA甲基化。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell Metabolism, Volume 10, Issue 3, 189-198, 2 September 2009 doi:10.1016/j.cmet.2009.07.011
Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density
Romain Barrès1,Megan E. Osler1,Jie Yan1,Anna Rune1,Tomas Fritz3,Kenneth Caidahl2,Anna Krook1,4andJuleen R. Zierath1,4,,
1 Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
2 Department of Molecular Medicine and Surgery, Section for Clinical Physiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
3 Centre of Family Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
4 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Epigenetic modification through DNA methylation isimplicated in metabolic disease. Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor (PPAR) coactivator-1α (PGC-1α) in diabetic subjects. Methylation levels were negatively correlated with PGC-1 mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1α was found within non-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor- (TNF-) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non-CpG methylation of PGC-1α and decreased mtDNA and PGC-1α mRNA. We provide evidence for PGC-1α hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1α promoter. |
