Elucidating the role of MeCP2 in the pathophysiology of obesity

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Project summary Obesity is a severely debilitating disease state that afflicts 650 million people worldwide. The increased prevalence of obesity is associated with a number of other diseases such as diabetes, cardiovascular disease, and hypertension. Given its implications for health care, it is now considered a global epidemic by the World Health Organization. These alarming statistics call for a need to understand neurobiological mechanisms that underlie the development of obesity. The goal of the current proposal is to understand the role that methyl- CpG-binding protein 2 (MeCP2) plays in the etiology of obesity. Recent studies implicate a role of this neuroepigenetic regulator in precipitating obesity in mouse models and in children diagnosed with Prader-Willi Syndrome, a neurodevelopmental disorder characterized by hyperphagia and marked obesity. The current proposal will utilize transgenic mouse models in which Mecp2 is knocked out in order to understand the neurobiological consequences of Cre-lox mediated knock out of this epigenetic factor in hypothalamic pro- opiomelanocortin (POMC) neurons. Another goal of this proposal is to understand how POMC-specific knockout of Mecp2 can alter behavioral responses to food. The data from this proposal will elucidate the role that MeCP2 plays on the development of obesity and may ultimately lead to therapeutic strategies with which to combat the obesity epidemic.