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DNA methylation: the pivotal interaction between early-life nutrition and glucose metabolism in later life

机译:DNA甲基化:早期营养和后期葡萄糖代谢之间的关键相互作用

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Traditionally, it has been widely acknowledged that genes together with adult lifestyle factors determine the risk of developing some metabolic diseases such as insulin resistance, obesity and diabetes mellitus in later life. However, there is now substantial evidence that prenatal and early-postnatal nutrition play a critical role in determining susceptibility to these diseases in later life. Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that exposures during early life play a critical role in determining the risk of developing metabolic diseases in adulthood. Currently, there are substantial epidemiological studies and experimental animal models that have demonstrated that nutritional disturbances during the critical periods of early-life development can significantly have an impact on the predisposition to developing some metabolic diseases in later life. The hypothesis that epigenetic mechanisms may link imbalanced early-life nutrition with altered disease risk has been widely accepted in recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic processes play a significant role in regulating tissue-specific gene expression, and hence alterations in these processes may induce long-term changes in gene function and metabolism that persist throughout the life course. The present review focuses on how nutrition in early life can alter the epigenome, produce different phenotypes and alter disease susceptibilities, especially for impaired glucose metabolism.
机译:传统上,人们普遍认为基因与成人生活方式因素共同决定了某些代谢性疾病(如胰岛素抵抗,肥胖症和糖尿病)在晚年发展的风险。但是,现在有大量证据表明,产前和产后早期营养在确定晚年对这些疾病的敏感性方面起着至关重要的作用。母体营养历来是决定子代健康的关键因素,而妊娠是影响子代生长发育的关键时间窗口。健康与疾病的发展起源(DOHaD)假说提出,生命早期的暴露对于确定成年后患代谢性疾病的风险起着至关重要的作用。当前,有大量的流行病学研究和实验动物模型表明,在生命早期发展的关键时期,营养失调会严重影响后期生命中某些代谢性疾病的易感性。近年来,表观遗传机制可能将早期营养失衡与疾病风险改变联系起来的假说已被广泛接受。表观遗传学可以定义为对基因表达中遗传性变化的研究,该变化不涉及DNA序列的改变。表观遗传过程在调节组织特异性基因表达中起着重要作用,因此这些过程中的改变可能会诱导基因功能和代谢的长期变化,并在整个生命过程中持续存在。本综述着重于早期的营养如何改变表观基因组,产生不同的表型和改变疾病的易感性,尤其是对于糖代谢受损的人。

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