Epigenetic Programming of Hypothalamic Pomc Regulates Feeding and Obesity

The environment can have a long-lasting influence on an individual’s physiology and behavior. While some environmental conditions can be beneficial and result in adaptive responses, others can lead to pathological behaviors (Franklin et al. Neuron 75:747–761, 2012). The period of perinatal development is one of the most critical windows during which adverse conditions can influence the growth and development of the fetus, as well as the offspring’s postnatal health and behavior (Franklin et al. Neuron 75:747–761, 2012). Moreover, recent evidence points to the possibility that changes which occur in the individual can sometimes pass between generations even if the offspring are not directly exposed to the stimulus (Gapp et al. Biology 36:491–502, 2014). Epigenetic alterations are prime candidates for the major molecular mechanism acting at the interface between genetic and environmental factors. Different studies showed that environmental factors, such as fetal alcohol exposure, maternal stress, under or overnutrition, or smoking exposure during sensitive periods affect gene expression in the offspring via altering epigenetic mechanisms, sometimes even across multiple generations (Begum et al. Endocrinology 154:4560–4569, 2013; Blaze and Roth Int J Dev Neurosci 31:804–810, 2013; Laufer et al. Dis Model Mech 6:977–992, 2013; Novakovic et al. Epigenetics 9, 2013). In this review, we discuss the involvement of the proopiomelanocortin (POMC) system, one of the most important regulators of energy balance, and describe how epigenetic changes such as histone modifications and DNA methylation modulate Pomc gene expression and function. We also summarize the recent findings from animal models which show that both diet-induced obesity (DIO) and malnutrition program the POMC system of subsequent generations via epigenetic mechanisms.