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

• 批准号: 10334111
• 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
• 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/10334111
• 关键词: Address; Adult; Affect; Animal Model; Award; Behavioral; Body Weight; Body Weight decreased; Calories; Cardiovascular Diseases; Child; Chronic; 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; Lead; 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; Palate; 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; Techniques; Therapeutic; Transgenic Mice; Underweight; Weight Gain; World Health Organization; base; 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

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 肥胖是一种严重的衰弱性疾病，困扰着全世界6.5亿人。增加的 肥胖症的流行与许多其它疾病如糖尿病，心血管疾病， 和高血压。鉴于其对卫生保健的影响，它现在被世界认为是一种全球流行病。 卫生组织。这些令人担忧的统计数据要求我们了解神经生物学机制， 是肥胖症发展的基础。本提案的目标是了解甲基- CpG结合蛋白2（MeCP 2）在肥胖的病因学中起作用。最近的研究表明， 神经表观遗传调节因子在小鼠模型和Prader-Willi综合征儿童中的促发性肥胖作用 综合征，一种以暴食和明显肥胖为特征的神经发育障碍。当前 该提案将利用Mecp 2被敲除的转基因小鼠模型，以了解 Cre-lox介导的敲除下丘脑前体中该表观遗传因子的神经生物学后果 阿黑皮素（POMC）神经元。本提案的另一个目标是了解POMC特定 敲除Mecp 2可以改变对食物的行为反应。本提案中的数据将阐明 MeCP 2在肥胖症的发展中起作用，并可能最终导致治疗策略， 来对抗肥胖症的流行。