Chromatin Modifications Associated With Diabetes and Obesity

Abstract

The incidence of obesity across the globe has doubled over the last several decades, leading to escalating rates of diabetes, cardiovascular disease and other complications. Given this dramatic rise in disease incidence, understanding the etiology of these diseases is therefore of paramount importance. Metabolic diseases such as obesity and diabetes result from a multitude of genetic and environmental factors. While 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 and obesity, which is the subject of this review.

Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies: The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group

“…Chromatin modifications have long been identified as important epigenomic markers involved in diseases and have been associated with multiple diseases such as cancer (Singh et al 2015; Su et al 2015), diabetes, and obesity (Schones et al 2015). Different sequencing methods have been developed to probe high-dimensional chromatin structures (Rao et al 2014) as well as chromatin-transcription factor interactions (Kellis et al 2014).…”

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

“…A range of 40% to 80% of cardiovascular diseases may be attributed to genetic factors (Webster et al, 2013). However, this genetic paradigm is challenged given the role for epigenetics in the control of not only cardiovascular homeostasis but also disease inheritability (Handy et al, 2011;Schones et al, 2015;Whayne, 2015;Yan & Marsden, 2015). Changes in ncRNA, DNA methylation patterns and histone structure have been shown to govern cardiovascular disease vulnerabilities (Thornburg, 2015), supporting the developmental origins of disease concept put forward by Prof. David Barker (Barker, 2004;Barker & Thornburg, 2013).…”

“…Profile of histone modifications to predict enhancer use in the colon in diet-induced and genetic obesity revealed close resemblance to colorectal cancer for the enhancer profile. Chronic inflammation associated with obesity is one potential mediator although high serum lipid levels associated with inflammation may also play a role (Schones et al, 2015). Another example is the similarity between vitamin B12 deficiency and multiple sclerosis in pathological traits, including conduction disturbances.…”

Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism

“…This control of gene expression includes post-translational modifications of the histone proteins used to package DNA and modification of the DNA itself, all without changing the underlying genetic code [50]. Epigenetics has emerged as a contributing pathway in both normal development as well as in the pathogenesis of a number of chronic diseases including obesity, diabetes, cancer, neurological disorders, and heart failure [51-54]. In this section we will focus on recent advances directly linking changes in the redox status of the cellular environment to specific mechanisms by which genes are regulated and then expand upon direct redox regulation within multiple pathways (Figure 1A).…”