State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
Antioxid Redox Signal. 2012 Jul 15;17(2):282-301. doi: 10.1089/ars.2011.4381. Epub 2012 Jan 13.
Epidemiological and animal studies have demonstrated a close link between maternal nutrition and chronic metabolic disease in children and adults. Compelling experimental results also indicate that adverse effects of intrauterine growth restriction on offspring can be carried forward to subsequent generations through covalent modifications of DNA and core histones.
DNA methylation is catalyzed by S-adenosylmethionine-dependent DNA methyltransferases. Methylation, demethylation, acetylation, and deacetylation of histone proteins are performed by histone methyltransferase, histone demethylase, histone acetyltransferase, and histone deacetyltransferase, respectively. Histone activities are also influenced by phosphorylation, ubiquitination, ADP-ribosylation, sumoylation, and glycosylation. Metabolism of amino acids (glycine, histidine, methionine, and serine) and vitamins (B6, B12, and folate) plays a key role in provision of methyl donors for DNA and protein methylation.
Disruption of epigenetic mechanisms can result in oxidative stress, obesity, insulin resistance, diabetes, and vascular dysfunction in animals and humans. Despite a recognized role for epigenetics in fetal programming of metabolic syndrome, research on therapies is still in its infancy. Possible interventions include: 1) inhibition of DNA methylation, histone deacetylation, and microRNA expression; 2) targeting epigenetically disturbed metabolic pathways; and 3) dietary supplementation with functional amino acids, vitamins, and phytochemicals.
Much work is needed with animal models to understand the basic mechanisms responsible for the roles of specific nutrients in fetal and neonatal programming. Such new knowledge is crucial to design effective therapeutic strategies for preventing and treating metabolic abnormalities in offspring born to mothers with a previous experience of malnutrition.
流行病学和动物研究表明，母体营养与儿童和成人的慢性代谢疾病密切相关。令人信服的实验结果还表明，宫内生长受限对后代的不利影响可以通过 DNA 和核心组蛋白的共价修饰传递给后代。
DNA 甲基化由 S-腺苷甲硫氨酸依赖性 DNA 甲基转移酶催化。组蛋白甲基转移酶、组蛋白去甲基酶、组蛋白乙酰转移酶和组蛋白去乙酰化酶分别催化组蛋白蛋白的甲基化、去甲基化、乙酰化和去乙酰化。组蛋白的活性也受磷酸化、泛素化、ADP-核糖基化、SUMO 化和糖基化的影响。氨基酸（甘氨酸、组氨酸、蛋氨酸和丝氨酸）和维生素（B6、B12 和叶酸）的代谢为 DNA 和蛋白质甲基化提供了甲基供体。
表观遗传机制的破坏会导致动物和人类的氧化应激、肥胖、胰岛素抵抗、糖尿病和血管功能障碍。尽管表观遗传学在代谢综合征的胎儿编程中起着公认的作用，但针对该疗法的研究仍处于起步阶段。可能的干预措施包括：1）抑制 DNA 甲基化、组蛋白去乙酰化和 microRNA 表达；2）针对表观遗传失调的代谢途径；3）用功能性氨基酸、维生素和植物化学物质进行饮食补充。
需要在动物模型中进行大量工作，以了解特定营养素在胎儿和新生儿编程中作用的基本机制。这种新知识对于设计预防和治疗母亲有营养不良史的后代代谢异常的有效治疗策略至关重要。
