Epigenetic epidemiology of obesity: application of epigenomic technology.
Epigenetic epidemiology of obesity: application of epigenomic technology.
复制标题
肥胖的表观遗传流行病学：表观基因组技术的应用。
DOI：
10.1111/j.1753-4887.2008.00060.x
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发表时间：
2008
影响因子：
6.1
通讯作者：
Waterland,RobertA
中科院分区：
文献类型：
--
作者：
Waterland,RobertA
令人信服的人类流行病学和动物模型数据表明，在哺乳动物产前和产后发育的关键时期，营养和其他环境刺激会影响发育途径，从而导致代谢和慢性疾病易感性的永久性变化。这种“代谢印记”背后的生物学机制尚不清楚，但可能涉及表观遗传机制。表观遗传学是研究非由DNA序列改变引起的基因表达潜力有丝分裂可遗传改变的学科。2发育过程中短暂的环境影响可导致表观遗传基因调控的永久性变化，越来越多的证据表明表观遗传失调与人类疾病有关。近几十年来，世界范围内肥胖发病率的上升速度太快，无法完全用遗传变异来解释，这表明其中涉及表观遗传机制。事实上，来自动物模型和人类的数据表明，表观遗传失调会导致肥胖。几年前Levin5提出，母亲在怀孕和哺乳期间的肥胖可能会导致后代神经网络的代谢印记，使肥胖易感性代代相传，甚至扩大。这一假设得到了最近对小鼠的研究的支持，这些研究表明，在出生后早期发育过程中，下丘脑投影的形成依赖于来自大脑外部的线索。瘦素缺乏（ob/ob）小鼠无法形成正常能量稳态所必需的下丘脑连接。值得注意的是，在出生后发育过程中，短暂的外源性瘦素可以拯救下丘脑神经支配并使成人体重正常化。类似地，母性
Compelling human epidemiologic and animal model data indicate that during critical periods of prenatal and postnatal mammalian development, nutrition and other environmental stimuli influence developmental pathways and thereby induce permanent changes in metabolism and chronic disease susceptibility. The biologic mechanisms underlying such ‘metabolic imprinting’are poorly understood, but epigenetic mechanisms are likely involved. 1 Epigenetics is the study of mitotically heritable alterations in gene expression potential that are not caused by changes in DNA sequence. 2 Transient environmental influences during development can cause permanent changes in epigenetic gene regulation, and accumulating evidence links epigenetic dysregulation to human disease. 3The worldwide increase in the prevalence of obesity in recent decades has occurred too rapidly to be explained completely by genetic variation, suggesting the involvement of epigenetic mechanisms. Indeed, data from animal models and humans demonstrate that epigenetic dysregulation can cause obesity. 4 Several years ago Levin5 proposed that maternal obesity during pregnancy and lactation might cause metabolic imprinting of neural networks in the offspring, perpetuating, or even amplifying, obesity susceptibility across generations. 5 This postulate is supported by recent studies in the mouse, which demonstrate that the formation of hypothalamic projections during early postnatal development is dependent upon cues from outside the brain. 6 Leptin-deficient (ob/ob) mice fail to form hypothalamic connections necessary for normal energy homeostasis. Remarkably, transient administration of exogenous leptin during postnatal development rescues hypothalamic innervation and normalizes adult body weight. 6 Analogously, maternal