Developmental origins of diabetes mellitus: Environmental epigenomics and emerging patterns.
Developmental origins of diabetes mellitus: Environmental epigenomics and emerging patterns.
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DOI：
10.1111/1753-0407.13403
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发表时间：
2023-07
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的流行病学证据表明，早期生活中的环境暴露在以后的生活中对糖尿病的易感性有一定的作用。此外，环境诱导的糖尿病易感性可传递给后代。表观遗传修饰提供了与环境因素和可能导致疾病表型的基因表达改变的潜在关联。在这里，我们带来了越来越多的证据表明，在发展早期的环境暴露与糖尿病通过表观遗传修饰。本文首先综述了环境因素对表观基因组进行修饰的表观遗传靶点，包括亚稳态表观等位基因和印记基因。然后，我们回顾了表观遗传学的变化，在关键的发育窗口，配子发生，胚胎发生，胎儿和出生后时期的环境挑战，与糖尿病易感性的具体例子。虽然其机制在很大程度上仍然未知，特别是在人类中，但新的研究方法现在逐渐可用，动物模型可以提供更深入的机制研究。这些都有影响调查的现象与人类糖尿病的联系，提供了一个新的视角环境引发的糖尿病风险。在生命早期，环境因素和表观基因组的相互作用，通过环境修饰的表观遗传标记，影响胰岛和外周胰岛素靶器官的转录谱，增加发展为糖尿病的易感性。环境获得的糖尿病表型和表观遗传修饰甚至可以通过影响生殖系表观基因组而跨代遗传，为糖尿病发病率的惊人增加提供了新的视角。虽然要应用于临床实践还有很长的路要走，但“成人糖尿病的发育起源”是糖尿病预防和干预的一个新兴的有希望的前景。 亮点
Mounting epidemiological evidence indicates that environmental exposures in early life have roles in diabetes susceptibility in later life. Additionally, environmentally induced diabetic susceptibility could be transmitted to subsequent generations. Epigenetic modifications provide a potential association with the environmental factors and altered gene expression that might cause disease phenotypes. Here, we bring the increasing evidence that environmental exposures early in development are linked to diabetes through epigenetic modifications. This review first summarizes the epigenetic targets, including metastable epialleles and imprinting genes, by which the environmental factors can modify the epigenome. Then we review the epigenetics changes in response to environmental challenge during critical developmental windows, gametogenesis, embryogenesis, and fetal and postnatal period, with the specific example of diabetic susceptibility. Although the mechanisms are still largely unknown, especially in humans, the new research methods are now gradually available, and the animal models can provide more in‐depth study of mechanisms. These have implications for investigating the link of the phenomena to human diabetes, providing a new perspective on environmentally triggered diabetes risk. Interactions of environmental factors and epigenome in early life, via environmentally modified epigenetic markers, affect the transcript profiles of pancreatic islets and peripheral insulin target organs, increasing the susceptibility of developing diabetes. Environmentally acquired diabetic phenotype and epigenetic modifications can even be inherited across generations via affecting germline epigenome, providing a new perspective on the alarming increase in diabetes incidence. Although there is a long way to applications for clinical practice, “developmental origins of adult diabetes” is an emerging promising perspective for diabetes prevention and intervention. Highlights
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影响因子：
4.8
作者：
Chen, Hui;Simar, David;Morris, Margaret J.
通讯作者：
Morris, Margaret J.
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Einstein FH
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