Lopomo A, Burgio E, Migliore L
Department of Translational Research and New Technologies in Medicine and Surgery, Medical Genetics Laboratories, University of Pisa, Pisa, Italy; Doctoral School in Genetics, Oncology, and Clinical Medicine; University of Siena; Siena, Italy.
European Cancer and Environment Research Institute (ECERI), Bruxelles, Belgium; ISDE International Society of Doctors for Environment (Scientific Office), Arezzo, Italy.
Prog Mol Biol Transl Sci. 2016;140:151-84. doi: 10.1016/bs.pmbts.2016.02.002.
Obesity is a metabolic disease, which is becoming an epidemic health problem: it has been recently defined in terms of Global Pandemic. Over the years, the approaches through family, twins and adoption studies led to the identification of some causal genes in monogenic forms of obesity but the origins of the pandemic of obesity cannot be considered essentially due to genetic factors, because human genome is not likely to change in just a few years. Epigenetic studies have offered in recent years valuable tools for the understanding of the worldwide spread of the pandemic of obesity. The involvement of epigenetic modifications-DNA methylation, histone tails, and miRNAs modifications-in the development of obesity is more and more evident. In the epigenetic literature, there are evidences that the entire embryo-fetal and perinatal period of development plays a key role in the programming of all human organs and tissues. Therefore, the molecular mechanisms involved in the epigenetic programming require a new and general pathogenic paradigm, the Developmental Origins of Health and Disease theory, to explain the current epidemiological transition, that is, the worldwide increase of chronic, degenerative, and inflammatory diseases such as obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. Obesity and its related complications are more and more associated with environmental pollutants (obesogens), gut microbiota modifications and unbalanced food intake, which can induce, through epigenetic mechanisms, weight gain, and altered metabolic consequences.
肥胖是一种代谢性疾病,正成为一个流行的健康问题:最近它已被定义为全球大流行。多年来,通过家族、双胞胎和收养研究的方法,人们已确定了单基因形式肥胖中的一些致病基因,但肥胖大流行的根源不能被认为主要是由遗传因素导致的,因为人类基因组不太可能在短短几年内发生变化。近年来,表观遗传学研究为理解肥胖大流行在全球范围内的传播提供了有价值的工具。表观遗传修饰——DNA甲基化、组蛋白尾部修饰和微小RNA修饰——在肥胖发生发展中的作用越来越明显。在表观遗传学文献中,有证据表明整个胚胎-胎儿期和围生期发育在所有人体器官和组织的编程中起着关键作用。因此,表观遗传编程所涉及的分子机制需要一种新的、通用的致病范式,即健康与疾病的发育起源理论,来解释当前的流行病学转变,也就是肥胖、糖尿病、心血管疾病、神经退行性疾病和癌症等慢性、退行性和炎症性疾病在全球范围内的增加。肥胖及其相关并发症越来越多地与环境污染物(致肥胖物)、肠道微生物群改变和不均衡的食物摄入有关,这些因素可通过表观遗传机制导致体重增加和代谢后果改变。