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Annu Rev Nutr. 2014;34:337-55. doi: 10.1146/annurev-nutr-071813-105315. Epub 2014 May 16.

Epigenetic mechanisms affecting regulation of energy balance: many questions, few answers.

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Departments of Pediatrics and Molecular & Human Genetics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, Texas 77030; email:


Extensive human and animal model data show that nutrition and other environmental influences during critical periods of embryonic, fetal, and early postnatal life can affect the development of body weight regulatory pathways, with permanent consequences for risk of obesity. Epigenetic processes are widely viewed as a leading mechanism to explain the lifelong persistence of such "developmental programming" of energy balance. Despite meaningful progress in recent years, however, significant research obstacles impede our ability to test this hypothesis. Accordingly, this review attempts to summarize progress toward answering the following outstanding questions: Is epigenetic dysregulation a major cause of human obesity? In what cells/tissues is epigenetic regulation most important for energy balance? Does developmental programming of human body weight regulation occur via epigenetic mechanisms? Do epigenetic mechanisms have a greater impact on food intake or energy expenditure? Does epigenetic inheritance contribute to transgenerational patterns of obesity? In each case, significant obstacles and suggested approaches to surmounting them are elaborated.


DNA methylation; energy expenditure; food intake; metabolic imprinting; obesity; programming

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