Ji Yun, Wu Zhenlong, Dai Zhaolai, Sun Kaiji, Wang Junjun, Wu Guoyao
State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China.
J Nutr Biochem. 2016 Jan;27:1-8. doi: 10.1016/j.jnutbio.2015.08.003. Epub 2015 Aug 10.
Recent findings from human and animal studies indicate that maternal undernutrition or overnutrition affects covalent modifications of the fetal genome and its associated histones that can be carried forward to subsequent generations. An adverse outcome of maternal malnutrition is the development of metabolic syndrome, which is defined as a cluster of disorders including obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension and insulin resistance. The transgenerational impacts of maternal nutrition are known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences (namely, epigenetics). The underlying mechanisms include chromatin remodeling, DNA methylation (occurring at the 5'-position of cytosine residues within CpG dinucleotides), histone modifications (acetylation, methylation, phosphorylation, ubiquitination and sumoylation) and expression and activity of small noncoding RNAs. The enzymes catalyzing these reactions include S-adenosylmethionine-dependent DNA and protein methyltransferases, DNA demethylases, histone acetylase (lysine acetyltransferase), general control nonderepressible 5 (GCN5)-related N-acetyltransferase (a superfamily of acetyltransferase) and histone deacetylase. Amino acids (e.g., glycine, histidine, methionine and serine) and vitamins (B6, B12 and folate) play key roles in provision of methyl donors for DNA and protein methylation. Therefore, these nutrients and related metabolic pathways are of interest in dietary treatment of metabolic syndrome. Intervention strategies include targeting epigenetically disturbed metabolic pathways through dietary supplementation with nutrients (particularly functional amino acids and vitamins) to regulate one-carbon-unit metabolism, antioxidative reactions and gene expression, as well as protein methylation and acetylation. These mechanism-based approaches may effectively improve health and well-being of affected offspring.
来自人类和动物研究的最新发现表明，孕期营养不足或营养过剩会影响胎儿基因组及其相关组蛋白的共价修饰，而这种影响可能会延续到后代。孕期营养不良的一个不良后果是代谢综合征的发生，代谢综合征被定义为一系列病症的集合，包括肥胖、高血糖、高胰岛素血症、高脂血症、高血压和胰岛素抵抗。孕期营养的跨代影响被称为胎儿编程，它是由DNA和组蛋白的共价修饰导致的基因表达的稳定且可遗传的改变所介导的（即表观遗传学），而DNA序列并无变化。潜在机制包括染色质重塑、DNA甲基化（发生在CpG二核苷酸中胞嘧啶残基的5'位置）、组蛋白修饰（乙酰化、甲基化、磷酸化、泛素化和类泛素化）以及小非编码RNA的表达和活性。催化这些反应的酶包括依赖S-腺苷甲硫氨酸的DNA和蛋白质甲基转移酶、DNA去甲基化酶、组蛋白乙酰转移酶（赖氨酸乙酰转移酶）、与一般控制非抑制因子5（GCN5）相关的N-乙酰转移酶（乙酰转移酶超家族）和组蛋白脱乙酰酶。氨基酸（如甘氨酸、组氨酸、蛋氨酸和丝氨酸）和维生素（B6、B12和叶酸）在为DNA和蛋白质甲基化提供甲基供体方面发挥着关键作用。因此，这些营养素及相关代谢途径在代谢综合征的饮食治疗中备受关注。干预策略包括通过膳食补充营养素（特别是功能性氨基酸和维生素）来靶向表观遗传紊乱的代谢途径，以调节一碳单位代谢、抗氧化反应和基因表达，以及蛋白质甲基化和乙酰化。这些基于机制的方法可能有效改善受影响后代的健康和福祉。
