Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
Mol Aspects Med. 2013 Jul-Aug;34(4):782-812. doi: 10.1016/j.mam.2012.06.010. Epub 2012 Jul 4.
Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding the importance of the inheritance of these epigenetic marks.
营养因素在人类健康中起着终身作用。事实上，越来越多的证据表明，营养物质和生物活性化合物影响代谢特征的机制之一是表观遗传学。食物成分与组蛋白修饰、DNA 甲基化、非编码 RNA 表达和染色质重塑因子之间的复杂相互作用导致了基因表达的动态调控，从而控制了细胞表型。尽管围产期是表型可塑性最高的时期，对发育编程有很大贡献，但在成年期也有证据表明营养对表观遗传调控有影响。与 2 型糖尿病、高血压、动脉粥样硬化和其他代谢紊乱一样，肥胖易感性和减肥结果与表观遗传模式的变化反复相关。通常伴随肥胖的不同非营养危险因素似乎也参与了这些表观遗传修饰，特别是高血糖、炎症、缺氧和氧化应激。目前，与肥胖相关的表观遗传学研究有三个主要目标：寻找表观遗传生物标志物来预测未来的健康问题或检测最易受影响的个体；了解可能通过影响表观遗传机制来调节基因表达的与肥胖相关的环境因素；以及研究基于营养或药理学制剂的新治疗策略，这些策略可以改变表观遗传标记。在这个层面上，主要任务是：开发体重调节的稳健表观遗传生物标志物，描述那些更容易受到饮食暴露影响的表观遗传标记，确定改变表观基因组的活性成分（和剂量），评估其他与肥胖相关因素对表观遗传调控的实际重要性，确定获得最佳结果的生命阶段，并了解这些表观遗传标记遗传的重要性。
