title: An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation.
abstract: In recent years, the etiology of human disease has greatly improved with the inclusion of epigenetic mechanisms, in particular as a common link between environment and disease. However, for most diseases we lack a detailed interpretation of the epigenetic regulatory pathways perturbed by environment and causal mechanisms. Here, we focus on recent findings elucidating nutrient-related epigenetic changes linked to obesity. We highlight studies demonstrating that obesity is a complex disease linked to disruption of epigenetically regulated metabolic pathways in the brain, adipose tissue and liver. These pathways regulate (1) homeostatic and hedonic eating behaviors, (2) adipocyte differentiation and fat accumulation, and (3) energy expenditure. By compiling these data, we illustrate that obesity-related phenotypes are repeatedly linked to disruption of critical epigenetic mechanisms that regulate key metabolic genes. These data are supported by genetic mutation of key epigenetic regulators, and many of the diet-induced epigenetic mechanisms of obesity are also perturbed by exposure to environmental toxicants. Identifying similarly perturbed epigenetic mechanisms in multiple experimental models of obesity strengthens the translational applications of these findings. We also discuss many of the ongoing challenges to understanding the role of environmentally induced epigenetic pathways in obesity and suggest future studies to elucidate these roles. This assessment illustrates our current understanding of molecular pathways of obesity that are susceptible to environmental perturbation via epigenetic mechanisms. Thus, it lays the groundwork for dissecting the complex interactions between diet, genes and toxicants that contribute to obesity and obesity-related phenotypes.
authors.affiliation: Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, USA; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd, Chapel Hill, NC 27599, United States; Department of Nutrition, 120 Mason Farm Rd, Chapel Hill, NC 27599, United States. Electronic address: folami@email.unc.edu.
authors.forename: Folami Y
authors.initials: FY
authors.lastname: Ideraabdullah
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity; D044127:Epigenesis, Genetic; D006801:Humans; D009765:Obesity / Q000209:etiology* / Q000235:genetics
chemical_list: D004785:Environmental Pollutants
keywords: Diet; Epigenetics; Metabolism; Nutrition; Obesity; Toxicant