Obesity, intergenerational programming, and epigenetics: emerging concepts and challenges
Chen, Michael Yung-Ray
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One of the most important medical and public health issues of today is obesity, defined as abnormal and excess fat accumulation. Obesity is linked to many health problems including metabolic syndrome (MS), hypertension, type II diabetes mellitus (T2DM), and cardiovascular disease (CVD). Recently, the incidence of these conditions has surged to epidemic proportions, especially in Western societies. Research has also linked obesity to cancer and osteoarthritis. Preventing, diagnosing, and treating obesity is challenging. The diagnosis of obesity is often unclear when it is made with generalized criteria such as the Body Mass Index (BMI). Obesity interventions generally include the often difficult lifestyle change to healthy diets and adequate exercise, which depends heavily upon patient compliance and discipline. Today's society is pushing for the discovery of a shortcut or of a "magic pill" to cure obesity. Consequently, many studies aim to identify therapeutic targets. The majority of current obesity research is focused on discovering and revealing the underlying mechanisms and genetic risk factors. Certain stages of development, such as childhood, are especially susceptible times to be exposed to stressors that lead to obesity. A developing concept is the intergenerational transmission of risk of obesity through epigenetics. Epigenetics is the study of the heritable changes in gene regulation and expression not caused by mutations or changes in DNA sequence. A person's genes may increase or decrease his or her susceptibility to obesity. In addition to genetic inheritance, parents may pass non-genetic alterations to their children. Changes can be mediated through methylation of deoxyribonucleic acids (DNA) and modifications to histones. These epigenetic changes may alter gene expression patterns and "program" offspring towards developing chronic metabolic disease. Many models have begun to show the effects of environmental perturbations on individuals and on several generations of future descendants. This review will analyze the current literature on obesity and evaluate this rapidly evolving field. Current obesity preventions and treatments will be surveyed. In addition, the relative impact of different contributors to obesity risk will be examined. The crossover between obesity and epigenetics may provide a deeper understanding of disease risk and developmental origins. Future directions of study will be proposed such as large-scale prospective studies to further characterize intergenerational transmission of risk.