An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation.
An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation.
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DOI：
10.1016/j.jnutbio.2015.09.002
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Ideraabdullah FY
中科院分区：
文献类型：
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作者：
Xue J;Ideraabdullah FY
近年来，随着表观遗传机制的纳入，人类疾病的病因学有了很大的改进，特别是作为环境和疾病之间的共同联系。然而，对于大多数疾病，我们缺乏对环境和因果机制干扰的表观遗传调控途径的详细解释。在这里，我们集中在最近的研究结果阐明营养相关的表观遗传变化与肥胖。我们强调研究表明，肥胖是一种复杂的疾病，与大脑，脂肪组织和肝脏中表观遗传调节代谢途径的破坏有关。这些途径调节（1）稳态和享乐饮食行为（2）脂肪细胞分化和脂肪积累，以及（3）能量消耗。通过汇编这些数据，我们说明了肥胖相关的表型反复与调节关键代谢基因的关键表观遗传机制的破坏有关。这些数据得到了关键表观遗传调节因子基因突变的支持，许多饮食诱导的肥胖表观遗传机制也受到环境毒物暴露的干扰。在多个肥胖实验模型中识别类似扰动的表观遗传机制加强了这些发现的转化应用。我们还讨论了许多正在进行的挑战，以了解环境诱导的表观遗传途径在肥胖症中的作用，并建议未来的研究来阐明这些作用。这项评估说明了我们目前对肥胖的分子途径的理解，这些分子途径易受环境干扰，通过表观遗传机制。因此，它奠定了基础，解剖之间的复杂的相互作用，饮食，基因和有毒物质，有助于肥胖和肥胖相关的表型。
In recent years, the etiology of human disease has greatly improved with the inclusion of epigenetic mechanisms, in particular as a common link between environment and disease. However, for most diseases we lack a detailed interpretation of the epigenetic regulatory pathways perturbed by environment and causal mechanisms. Here, we focus on recent findings elucidating nutrient-related epigenetic changes linked to obesity. We highlight studies demonstrating that obesity is a complex disease linked to disruption of epigenetically regulated metabolic pathways in the brain, adipose tissue and liver. These pathways regulate (1) homeostatic and hedonic eating behaviors (2) adipocyte differentiation and fat accumulation, and (3) energy expenditure. By compiling these data we illustrate that obesity-related phenotypes are repeatedly linked to disruption of critical epigenetic mechanisms that regulate of key metabolic genes. These data are supported by genetic mutation of key epigenetic regulators and many of the diet induced epigenetic mechanisms of obesity are also perturbed by exposure to environmental toxicants. Identifying similarly perturbed epigenetic mechanisms in multiple experimental models of obesity strengthens the translational applications of these findings. We also discuss many of the ongoing challenges to understanding the role of environmentally-induced epigenetic pathways in obesity and suggest future studies to elucidate these roles. This assessment illustrates our current understanding of molecular pathways of obesity that are susceptible to environmental perturbation via epigenetic mechanisms. Thus, it lays the groundwork for dissecting the complex interactions between diet, genes, and toxicants that contribute to obesity and obesity-related phenotypes.