Developmental Origins of Health and Disease Division, Institute of Developmental Sciences, University of Southampton School of Medicine, Southampton, UK.
Toxicol Mech Methods. 2011 May;21(4):353-61. doi: 10.3109/15376516.2011.559370.
The metabolic syndrome (MetS) represents a cluster of cardiometabolic risk factors, including central obesity, insulin resistance, glucose intolerance, dyslipidemia, hypertension, hyperinsulinemia and microalbuminuria, and more recently, nonalcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome (PCOS) and atherosclerosis. Although the concept of the MetS is subject to debate due to lack of a unifying underlying mechanism, the prevalence of a metabolic syndrome phenotype is rapidly increasing worldwide. Moreover, it is increasingly prevalent in children and adolescents of obese mothers. Evidence from both epidemiological and experimental animal studies now demonstrates that MetS onset is increasingly likely following exposure to suboptimal nutrition during critical periods of development, as observed in maternal obesity. Thus, the developmental priming of the MetS provides a common origin for this multifactorial disorder. Consequently, the mechanisms leading to this developmental priming have recently been the subject of intensive investigation. This review discusses recent data regarding the epigenetic modifications resulting from nutrition during early development that mediate persistent changes in the expression of key metabolic genes and contribute toward an adult metabolic syndrome phenotype. In addition, this review considers the role of the endogenous molecular circadian clock system, which has the potential to act at the interface between nutrient sensing and epigenetic processing. A continued and greater understanding of these mechanisms will eventually aid in the identification of individuals at high risk of cardiovascular disease (CVD) and type 2 diabetes, and help develop therapeutic interventions, in accordance with current global government strategy.
代谢综合征（MetS）代表了一组心血管代谢危险因素，包括中心性肥胖、胰岛素抵抗、葡萄糖耐量受损、血脂异常、高血压、高胰岛素血症和微量白蛋白尿，以及最近的非酒精性脂肪性肝病（NAFLD）、多囊卵巢综合征（PCOS）和动脉粥样硬化。尽管由于缺乏统一的潜在机制，代谢综合征的概念存在争议，但代谢综合征表型的患病率在全球范围内迅速增加。此外，肥胖母亲的儿童和青少年中也越来越普遍。来自流行病学和实验动物研究的证据现在表明，在发育关键期暴露于次优营养后，代谢综合征的发病风险越来越高，正如肥胖母亲所观察到的那样。因此，代谢综合征的发育启动为这种多因素疾病提供了共同的起源。因此，导致这种发育启动的机制最近成为了密集研究的主题。这篇综述讨论了最近关于早期发育过程中营养引起的表观遗传修饰的数据，这些修饰介导了关键代谢基因表达的持久变化，并导致了成年代谢综合征表型。此外，这篇综述还考虑了内源性分子昼夜节律系统的作用，该系统有可能在营养感应和表观遗传处理之间发挥作用。对这些机制的进一步了解将有助于最终确定处于心血管疾病（CVD）和 2 型糖尿病高风险的个体，并根据当前全球政府战略帮助开发治疗干预措施。
