Citation: Zhang Y, Cerjak D, Ali O. Finding Epigenetic Determinants of the Metabolic Syndrome. Austin J Endocrinol Diabetes. 2014;1(6): 1029. Austin J Endocrinol Diabetes - Volume 1 Issue 6 - 2014 ISSN : 2381-9200 | www.austinpublishinggroup.com Zhang et al. © All rights are reserved Austin Journal of Endocrinology and Diabetes Open Access Abstract Metabolic Syndrome (MetS) substantially increases one’s risk for type 2 diabetes (T2D) and cardiovascular disease. It now affects more than one third of adults in the U.S. and has similar impact on other societies globally. Results from recent genome-wide association studies (GWAS) have suggested that the inherited variance in anindividuals’risk of expressing MetS traits cannot be completely explained by variation in the primary sequence of the genome; mechanisms beyond the genetic sequence variants are increasingly compelling for researchers in the ield. Epigenetic modiications such as DNA methylation and histone modiications are hypothesized to play important roles in the pathophysiology of diseases including MetS and may explain some of the missing heritability. Recent pilot studies conducted in humans and animals have also suggested epigenetic changes such as CpG methylation modify one’s susceptibility to developing MetS in response to prenatal and postnatal environmental exposures. Although these indings are intriguing, more work is needed in order to unravel a map of epigenetic determinants of MetS. Keywords: Metabolic Syndrome; DNA Methylation; Epigenetic; Obesity; Environmental Cues study population [16]. It is also known that the atherosclerotic process starts in childhood and is accelerated in individuals who are insulin resistant, dyslipidemic and/or show signs of systemic inlammation [17-19]. At a molecular level, the mechanisms by which obesity leads to the development of insulin resistance, dyslipidemia and associated phenotypes are poorly understood but necessarily involve long-term changes in genetic regulation and gene expression. Since the underlying DNA sequence remains unchanged, these changes in gene regulation and function must be mediated by epigenetic mechanisms. hese mechanisms, including methylation of CpG sites of DNA, are some of the most important processes by which genetic function is regulated and altered by development and by the external environment [20-26]. Why study epigenetic in MetS Epigenetic mechanisms, which involve DNA and histone modiications, mediate the interaction between gene and environment throughout the lifespan; while the underlying genetic sequence does not change, environmental inluences can alter epigenetic marks and thus alter gene expression and induce long term changes in phenotype and disease susceptibility [27]. he gradual accumulation of epigenetic changes in critical genes may contribute to the observed age-related increase in the prevalence of various chronic disorders [28-31]. Epigenetic changes are known to be heritable across more than one generation of ofspring in plants and mammals [32-37] and there is evidence that transgenerational epigenetic inheritance also occurs in humans [38-41]. Such transgenerational inheritance of epigenetic states may contribute to the observed inherited risk of various chronic disorders, including metabolic disorders [42]. DNA methylation is one of the most extensively studied epigenetic mechanisms and plays an important role in the process Introduction Chronic diseases such as cancer, type 2 diabetes (T2D), metabolic syndrome (MetS), cardiovascular disease and dementia constitute the most common health problems seen in developed societies (increasingly, in developing societies) and their prevalence increases with age in all populations [1-4]. It is well established that environmental exposures, especially in early life, can alter the risk of various chronic diseases later in life [5, 6] and while the mechanisms involved in this “programming” of future risk are not yet understood in detail, epigenetic changes are believed to play an important role in this process [7, 8]. Epigenetic mechanisms are also postulated to be involved in modifying the risk of MetS secondary to postnatal exposures and may explain the “missing heritability” of chronic diseases like MetS. In this mini-review, we discuss the historical context of the concept of MetS epigenetic, the recent evidence and our current opinions about this rising ield. The Metabolic Syndrome he Metabolic Syndrome (MetS) is a form of obesity characterized by a cluster of phenotypes that includes increased abdominal fat mass, impaired insulin responsiveness, dyslipidemia with increased plasma triglycerides and decreased HDL-cholesterol, increased blood pressure and elevated circulating cytokines and adipokines [9]. It is estimated to afect 34% of adult Americans [10] and adds an extra $2,000 per person in annual health care costs [11]. Its prevalence is low in childhood and increases with advancing age [12, 13]. he prevalence of MetS-associated cardiovascular (CV) risk factors is relatively low during early childhood but increases during adolescence and thereater tends to persist into adulthood [12-15]. We have observed a similar trend in adolescents in our cross-sectional Mini Review Finding Epigenetic Determinants of the Metabolic Syndrome Zhang Y 1 *, Cerjak D 1 , Ali O 2 1 Department of Medicine, Medical College of Wisconsin, USA 2 Department of Pediatrics, Medical College of Wisconsin, USA *Corresponding author: Zhang Y, Department of Medicine, Medical College of Wisconsin, USA, Tel: 414- 955-4013; Fax: 414-955-6386; Email: yzhang@mcw.edu Received: October 03, 2014; Accepted: November 21, 2014; Published: November 27, 2014