Elucidating the role of MeCP2 in the pathophysiology of obesity

阐明 MeCP2 在肥胖病理生理学中的作用

基本信息

批准号：
10662185
负责人：
Elisa S Na
金额：
$ 29.55万
依托单位：
TEXAS WOMAN'S UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-08 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10662185
关键词：
Address Adult Affect Animal Model Award Behavioral Body Weight Body Weight decreased Calories Cardiovascular Diseases Child Chronic Classification Clinical Data Data Desire for food Diabetes Mellitus Diagnosis Disease Eating Electrophysiology (science)Epidemic Epigenetic Process Etiology Failure Fatty acid glycerol esters Food Functional disorder Goals Grant Healthcare High Fat Diet Homeostasis Hyperphagia Hypertension Hypothalamic structure Individual Kidney Diseases Knock-out Knockout Mice Leptin Liver diseases Malignant Neoplasms MeCP2 Duplication Syndrome Mediating Metabolism Methyl-CpG-Binding Protein 2 Mind Molecular Molecular Biology Morbid Obesity Mus Mutation Neurobiology Neurodevelopmental Disorder Neurologic Neurons Obesity Obesity Epidemic Overweight Persons Phenotype Play Prader-Willi Syndrome Prevalence Pro-Opiomelanocortin Process Productivity Property Prosencephalon Recurrent disease Research Rett Syndrome Rewards Risk Factors Role Secure Signal Pathway Signal Transduction Syndrome Techniques Therapeutic Transgenic Mice Underweight Weight Gain World Health Organization behavioral response combat effective therapy food quality gain of function mutation hedonic insight knock-down loss of function mutation male mouse model neurobiological mechanism neuronal excitability obesity development preference reward processing statistics therapeutic target treatment strategy

项目摘要

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.

项目摘要肥胖是一种严重使人衰弱的疾病状态，在全球范围内遭受6.5亿人的困扰。增加肥胖症患病率与许多其他疾病有关，例如糖尿病，心血管疾病，和高血压。鉴于它对医疗保健的影响，它现在被世界视为全球流行病卫生组织。这些令人震惊的统计数据要求需要了解神经生物学机制肥胖的发展是基础。当前建议的目的是了解甲基的作用 CpG结合蛋白2（MECP2）在肥胖症的病因中发挥作用。最近的研究暗示了这一点在小鼠模型和被诊断患有prader-willi的儿童中，神经毛皮调节剂在沉淀肥胖症中综合征是一种以肉质和明显肥胖为特征的神经发育障碍。电流建议将利用转基因鼠标模型，其中MECP2被淘汰以了解 Cre-lox介导的神经生物学后果从下丘脑促进中的这种表观遗传因素中淘汰 Opiomelanocortin（POMC）神经元。该提案的另一个目标是了解POMC特定的 MECP2的敲除可以改变对食物的行为反应。该提案的数据将阐明角色 MECP2在肥胖的发展方面发挥了作用，最终可能导致治疗策略打击肥胖流行。