Maternal obesity and fetal metabolic programming: a fertile epigenetic soil
Maternal obesity and fetal metabolic programming: a fertile epigenetic soil
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DOI：
10.1152/ajpregu.00310.2010
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发表时间：
2010-09-01
影响因子：
2.8
通讯作者：
Friedman, Jacob E.
中科院分区：
文献类型：
--
作者：
Heerwagen, Margaret J. R.;Miller, Melissa R.;Friedman, Jacob E.
Heerwagen MJR，米勒MR，Barcelona LA，Friedman JE.母体肥胖和胎儿代谢程序：肥沃的表观遗传土壤。Am J Physiol Regul Integr Comp Physiol 299：R711-R722，2010年。首次发表于2010年7月14日; doi：10.1152/ajpregu.00310.2010。肥胖和超重的发生率在美国和世界范围内的发达国家已经达到流行病的水平。更令人震惊的是，幼儿和青少年的代谢性疾病发病率越来越高。肥胖、超重和糖尿病母亲所生的婴儿（即使体重正常）肥胖增加，后期代谢疾病的风险增加。除了母亲的葡萄糖，高脂血症和炎症可能有助于通过胎儿代谢程序的儿童肥胖症的流行，其机制还不清楚。妊娠前肥胖，当与母体代谢的正常变化相结合时，可能会放大炎症和血脂的增加，这可能对发育中的胚胎和子宫内的胎儿产生深远的影响。胎儿暴露于过量的血脂，特别是饱和脂肪酸，可以激活促炎途径，这可能会影响底物代谢和线粒体功能，以及干细胞的命运，所有这些都会影响器官发育和对出生后环境的反应。胎儿和新生儿生命的特点是具有巨大的可塑性和通过表观遗传修饰改变基因表达水平来响应环境因素（营养素、氧气、激素）的能力。鉴于脂质作为转录激活因子和信号分子，过量的胎儿脂质暴露可能通过表观遗传机制调节参与脂质传感和代谢的基因。基因表达的表观遗传调控的特征在于对DNA和染色质的共价修饰，其改变基因表达而不依赖于基因序列。表观遗传修饰可以通过正反馈和负反馈循环来维持，从而在代谢基因及其主要转录调节因子的表达中产生稳定的变化。本文的目的是回顾目前的文献对母亲-胎儿的脂质代谢和母亲肥胖的结果，并提出一些潜在的机制，胎儿代谢规划的关键器官系统，调节出生后的能量平衡，重点是表观遗传学和宫内环境。
Heerwagen MJR, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol 299: R711-R722, 2010. First published July 14, 2010; doi:10.1152/ajpregu.00310.2010.-The incidence of obesity and overweight has reached epidemic levels in the United States and developed countries worldwide. Even more alarming is the increasing prevalence of metabolic diseases in younger children and adolescents. Infants born to obese, overweight, and diabetic mothers (even when normal weight) have increased adiposity and are at increased risk of later metabolic disease. In addition to maternal glucose, hyperlipidemia and inflammation may contribute to the childhood obesity epidemic through fetal metabolic programming, the mechanisms of which are not well understood. Pregravid obesity, when combined with normal changes in maternal metabolism, may magnify increases in inflammation and blood lipids, which can have profound effects on the developing embryo and the fetus in utero. Fetal exposure to excess blood lipids, particularly saturated fatty acids, can activate proinflammatory pathways, which could impact substrate metabolism and mitochondrial function, as well as stem cell fate, all of which affect organ development and the response to the postnatal environment. Fetal and neonatal life are characterized by tremendous plasticity and the ability to respond to environmental factors (nutrients, oxygen, hormones) by altering gene expression levels via epigenetic modifications. Given that lipids act as both transcriptional activators and signaling molecules, excess fetal lipid exposure may regulate genes involved in lipid sensing and metabolism through epigenetic mechanisms. Epigenetic regulation of gene expression is characterized by covalent modifications to DNA and chromatin that alter gene expression independent of gene sequence. Epigenetic modifications can be maintained through positive and negative feedback loops, thereby creating stable changes in the expression of metabolic genes and their main transcriptional regulators. The purpose of this article is to review current literature on maternal-fetal lipid metabolism and maternal obesity outcomes and to suggest some potential mechanisms for fetal metabolic programming in key organ systems that regulate postnatal energy balance, with an emphasis on epigenetics and the intrauterine environment.