Chapter 11 - Epigenetics and Obesity

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The etiology of obesity is multifactorial, involving complex interactions among the genetic makeup, neuroendocrine status, fetal programming, and different unhealthy environmental factors, such as sedentarism or inadequate dietary habits. Among the different mechanisms causing obesity, epigenetics, defined as the study of heritable changes in gene expression that occur without a change in the DNA sequence, has emerged as a very important determinant. Experimental evidence concerning dietary factors influencing obesity development through epigenetic mechanisms has been described. Thus, identification of those individuals who present with changes in DNA methylation profiles, certain histone modifications, or other epigenetically related processes could help to predict their susceptibility to gain or lose weight. Indeed, research concerning epigenetic mechanisms affecting weight homeostasis may play a role in the prevention of excessive fat deposition, the prediction of the most appropriate weight reduction plan, and the implementation of newer therapeutic approaches.

Section snippets

Genes, the Environment, and Their Roles and Interactions in Obesity

Excessive fat accumulation and obesity conditions depend not only on the genetic makeup controlling energy balance, but also on lifestyle and perinatally programmed behavior. In this context, the impact of environmental agents (poor dietary and activity patterns), fetal programming, and even assortative mating could also result in a genetic predisposition and likely play a part in the obesity epidemic. Indeed, it has been hypothesized that the maintenance of body weight and composition depends

Methods for Epigenome Study of Obesity

The arsenal of genomic assays available and the rapid technological developments concerning next-generation molecular techniques have made possible multiple approaches to study epigenetics and obesity. These technologies range from classical molecular biology (Western blot, RT-PCR) to the most recent genome wide association screens. Thus, depending on the epigenetic question to be investigated (DNA methylation, covalent histone modifications, enzymes involved in modifications, polycombs,

Fetal Programming and Epigenetics

The fetal or developmentally programmed origins of adult disease hypothesis states that environmental factors and maternal lifestyles, particularly nutrition, act in early life to drive the risks for the onset of metabolic diseases including cardiovascular events, insulin resistance, and excessive weight gain in later life stages.60 These relationships between adult diseases and perinatal nutritional status were initially identified through epidemiological strategies, but further confirmed and

DNA Methylation

Epigenetic mechanisms can be controlled by dietary compounds, metabolic state, endocrine impairments, and diseases, all of them keys in the development, comorbidities, and treatment of obesity.66 Early studies of DNA methylation postulated possible effects of one-carbon compounds on methyltransferases action. DNA and HMTs all use S-adenosylmethionine (SAM) as a methyl donor,47 its bioavailability being directly influenced by the diet. SAM is formed from methyl groups derived from choline,

Fetal and Early Postnatal Life Influence on Future Obesity Risk

It is becoming clear that epigenetics is a significant contributor to obesity incidence and other related diseases.22, 66 Recent studies have highlighted the importance of adverse perinatal environments, during pregnancy or lactation, in the future development of obesity, suggesting that mother's nutrition or lifestyle choices could alter the developmental programming of the fetus.214 The role of nutrition in adulthood in modifying the epigenetic patterns of DNA and their possible transmission

Genetics and Epigenetics of Obesity: Epiobesogenes

Continuous scientific advances promote understanding of the implication of genetic and epigenetic mechanisms in the development and therapy of several important diseases, such as cancer, type 2 diabetes, and obesity.263, 264, 265 The heritability estimates for obesity are high compared with other complex diseases.266 Thus, multigenic interactions are more relevant to human obesity, for which the genetic contribution has been estimated to account for 25–80% of the variability in weight gain.267

Concluding Remarks

Obesity is a multifactorial disorder characterized by a disproportionately high adipose tissue mass, associated with a disequilibrium in the energy balance equation.9 Today's view is that a large fraction of body weight variability is under genetic control and that the growing prevalence of obesity is the result of the interaction of a genetic susceptibility with inadequate lifestyles (increases in consumption of foods rich in carbohydrates and fats and reduction in physical activity level,

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