Elucidating the role of MeCP2 in the pathophysiology of obesity

项目总结 肥胖是一种严重使人虚弱的疾病，全球有6.5亿人患有肥胖症。增加的 肥胖的流行与许多其他疾病有关，如糖尿病、心血管疾病、 还有高血压。鉴于它对医疗保健的影响，它现在被世界认为是一种全球流行病 卫生组织。这些令人震惊的统计数据要求我们有必要了解 是肥胖症发展的基础。当前提案的目标是了解甲基- CpG结合蛋白2(MeCP2)在肥胖的病因中起作用。最近的研究表明，这一点与 神经表观遗传调节因子在小鼠肥胖模型和诊断为Prader-Willi儿童中的作用 综合症，一种神经发育障碍，以吞噬过多和明显肥胖为特征。海流 该提案将利用MeCP2基因敲除的转基因小鼠模型来了解 Cre-lox介导的这种表观遗传因子敲除对下丘脑前体的神经生物学影响 阿片黑素皮质素(POMC)神经元。这项提案的另一个目标是了解POMC特定于 MeCP2基因敲除可以改变对食物的行为反应。这项提案中的数据将阐明 MeCP2在肥胖症的发展过程中发挥作用，并最终可能导致治疗策略 以对抗肥胖症的流行。

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.