Epigenetics and Metabolism in Health and Disease

Epigenetics and Metabolism in Health and Disease

Abstract
In the next 10 years, one billion people are estimated to suffer from disabling consequences of metabolic disorders, making them the number one noncommunicable disease on a global scale by 2030. Lots of risk factors such as dietary intake, lack of exercise and other life style behaviors are considered to play a role in the development of metabolic disorders. Despite the efforts that have been undertaken to unravel their potential causes, the underlying molecular mechanisms remain elusive. Evidence suggests that the pathogenesis involves changes on chromatin and chromatin-modifying enzymes, which can contribute to a persistent dysregulated metabolic phenotype. Indeed, a rising number of studies links epigenetic alterations with the diagnosis and prognosis of metabolic disorders. A prerequisite for exploiting these findings for pharmacological intervention is a detailed understanding of how differential epigenetic modifications control cell metabolism. In this mini review, we summarize the recent advances in uncovering the interplay between epigenetics and metabolic pathways on a cellular level and highlight potential new avenues for alternative treatment strategies.

Introduction
Noncommunicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide (WHO, 2017). Metabolic diseases constitute the greatest part of NCDs and according to the International Diabetes Federation (IDF) atlas for 2017, more than 693 million people will be suffering from diabetes by 2045 (IDF, 2017). Obesity and cardiovascular diseases are rising (WHO, 2014) with the prevalence of obesity projected to 1 billion people worldwide by 2030 (Kelly et al., 2008). A group of risk factors such as high fasting blood sugar, high blood pressure, low HDL cholesterol level and others are defined as the “metabolic syndrome," which is thought to predict or increase the risk for diabetes and heart diseases (NIH, 2016). These data emphasize the urgent need to find better prevention methods and therapies for the metabolic syndrome. However, many questions remain unanswered about the pathology of the metabolic diseases and factors such as life style behavior like nutrition habits and training routine are considered to play a role in the development of the diseases across different patients (Jumpertz von Schwartzenberg and Turnbaugh, 2015; Zeevi et al., 2015; Khera et al., 2016; Phillips, 2016). The molecular mechanisms that frame the influence of metabolism on possible gene deregulation patterns, underpinning causality and onset of metabolic diseases, are far from being fully understood. Epigenetics and metabolism trade interacting factors dynamically and reciprocally, while constantly being modulated by multifactorial external stimuli, unfolding correlations among different pathological conditions. In addition to immediate physiological effects like hormonal dysregulation and generation of adipose tissue, life style factors and food intake in particular may also affect the epigenome. For instance, there is strong evidence that nutritional habits can influence gene transcription epigenetically (van Dijk et al., 2015; Etchegaray and Mostoslavsky, 2016) and there are several studies claiming inheritance to the offspring (Figure ​Figure11) (Seki et al., 2012; Nicholas et al., 2013; Rando and Simmons, 2015). A recent genome wide analysis of DNA methylation in children born to parents affected by the Dutch famine showed that 70 years later several DNA regions associated with growth and metabolism were significantly differentially methylated, including genes involved in control of birth weight and LDL cholesterol in later life (Tobi et al., 2015).