Schones Dustin E, Leung Amy, Natarajan Rama
From the Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA.
Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1557-61. doi: 10.1161/ATVBAHA.115.305041. Epub 2015 Jun 4.
The incidence of obesity across the globe has doubled over the past several decades, leading to escalating rates of diabetes mellitus, cardiovascular disease, and other complications. Given this dramatic rise in disease incidence, understanding the cause of these diseases is therefore of paramount importance. Metabolic diseases, such as obesity and diabetes mellitus, result from a multitude of genetic and environmental factors. Although the genetic basis of these diseases has been extensively studied, the molecular pathways whereby environmental factors influence disease progression are only beginning to be understood. One manner by which environmental factors can contribute to disease progression is through modifications to chromatin. The highly structured packaging of the genome into the nucleus through chromatin has been shown to be fundamental to tissue-specific gene regulation. Modifications to chromatin can regulate gene expression and are involved in a myriad of biological functions, and hence, disruption of these modifications is central to many human diseases. These modifications can furthermore be epigenetic in nature, thereby contributing to prolonged disease risk. Recent work has demonstrated that modifications to chromatin are associated with the progression of both diabetes mellitus and obesity, which is the subject of this review.
在过去几十年间,全球肥胖症的发病率翻了一番,导致糖尿病、心血管疾病及其他并发症的发生率不断攀升。鉴于疾病发病率的急剧上升,了解这些疾病的病因至关重要。肥胖症和糖尿病等代谢性疾病是由多种遗传和环境因素导致的。尽管对这些疾病的遗传基础已进行了广泛研究,但环境因素影响疾病进展的分子途径才刚刚开始被了解。环境因素促进疾病进展的一种方式是通过对染色质的修饰。基因组通过染色质高度结构化地包装进细胞核已被证明是组织特异性基因调控的基础。对染色质的修饰可调节基因表达,并参与众多生物学功能,因此,这些修饰的破坏是许多人类疾病的核心。此外,这些修饰本质上可能是表观遗传的,从而增加了长期患病风险。最近的研究表明,染色质修饰与糖尿病和肥胖症的进展都有关联,这也是本综述的主题。