The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, Denmark.
Department of Molecular Medicine and Department of Physiology and Pharmacology, Section of Integrative Physiology, Karolinska Institutet, von Eulers väg 4a, SE 171 77 Stockholm, Sweden.
Nat Rev Endocrinol. 2016 Aug;12(8):441-51. doi: 10.1038/nrendo.2016.87. Epub 2016 Jun 17.
Epigenetic changes are caused by biochemical regulators of gene expression that can be transferred across generations or through cell division. Epigenetic modifications can arise from a variety of environmental exposures including undernutrition, obesity, physical activity, stress and toxins. Transient epigenetic changes across the entire genome can influence metabolic outcomes and might or might not be heritable. These modifications direct and maintain the cell-type specific gene expression state. Transient epigenetic changes can be driven by DNA methylation and histone modification in response to environmental stressors. A detailed understanding of the epigenetic signatures of insulin resistance and the adaptive response to exercise might identify new therapeutic targets that can be further developed to improve insulin sensitivity and prevent obesity. This Review focuses on the current understanding of mechanisms by which lifestyle factors affect the epigenetic landscape in type 2 diabetes mellitus and obesity. Evidence from the past few years about the potential mechanisms by which diet and exercise affect the epigenome over several generations is discussed.
表观遗传变化是由基因表达的生化调节剂引起的，这些调节剂可以在代际之间或通过细胞分裂传递。表观遗传修饰可以来自各种环境暴露，包括营养不良、肥胖、体力活动、压力和毒素。整个基因组的短暂表观遗传变化可以影响代谢结果，并且可能是或可能不是可遗传的。这些修饰指导并维持细胞类型特异性基因表达状态。短暂的表观遗传变化可以由 DNA 甲基化和组蛋白修饰来驱动，以响应环境应激源。对胰岛素抵抗和运动适应性反应的表观遗传特征的详细了解可能会确定新的治疗靶点，这些靶点可以进一步开发以提高胰岛素敏感性并预防肥胖。本综述重点介绍了生活方式因素影响 2 型糖尿病和肥胖症中表观遗传景观的机制的现有认识。讨论了过去几年关于饮食和运动如何通过几代人影响表观基因组的潜在机制的证据。
