Regulation of Food Intake and Body Weight by Brain Apo E

大脑 Apo E 对食物摄入量和体重的调节

基本信息

批准号：
7201824
负责人：
Min Liu
金额：
$ 28.78万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7201824
关键词：
Address Affect Amino Acids Animal Model Animals Antibodies Apolipoprotein E Appetite Depressants Appetitive Behavior Area Behavioral Biochemical Blocking Antibodies Body Weight Brain Cardiovascular Diseases Consumption Data Desire for food Development Eating Energy Metabolism Environment Epidemic Equilibrium Equipment Etiology Faculty Feeding behaviors Food Food Intake Regulation Genes Goals Health Health Care Costs Homeostasis Hypothalamic structure Individual Investigation Knockout Mice Knowledge LDL-Receptor Related Protein 1 Leptin Lipids Lipoproteins Liver Malaise Measures Mediating Metabolism Methods Molecular Mus Natural regeneration Neuraxis Neuropeptides Neurosciences Obesity Outcome Outcome Study Outcomes Research Pathway interactions Peripheral Physiological Play Positioning Attribute Preventive Principal Investigator Production Protein Biosynthesis Proteins Publishing Range Rattus Receptor Signaling Reporting Research Research Personnel Resources Risk Factors Role Satiation Signal Transduction Signal Transduction Pathway System Therapeutic Intervention Tissues Toxic effect United States Universities Water consumption Weight maintenance regimen Wild Type Mouse Work base cholesterol transporters diabetes risk field study food consumption innovation insight knockout gene lipid transport member neuroprotection novel obesity prevention prevent programs receptor

项目摘要

DESCRIPTION (provided by applicant): Apolipoprotein E (apoE) is produced abundantly in the liver and brain. It plays important roles in the metabolism and redistribution of lipids. In the brain, apoE has been implicated in development, regeneration, and neuroprotection. Recently, we have identified a novel function of apoE, i.e. centrally administered apoE potently suppresses food intake and body weight without eliciting signs of toxicity, and blocking the action of endogenous brain apoE with its specific antibody increases food intake. Mice with a targeted deletion of the apoE gene consume more food and weigh more than wild-type mice. These results imply that apoE plays an essential role in the control of food intake and body weight. Thus, we speculate that insufficient apoE production may render an animal vulnerable to the development of obesity. Our long-term goal is to identify pharmacological targets for suppressing appetite as a means of preventing and treating obesity. The objective of this specific application is to identify the mechanism(s) mediating apoE's effect in the control of food intake and body weight. The first specific aim will assess the hypothesis that increased food consumption in obese animals is due in part to reduced apoE signaling in the hypothalamus, a central area regulating energy homeostasis. The second specific aim will evaluate the hypothesis that hypothalamic apoE exerts its anorectic function by influencing catabolic regulatory neuropeptides and/or their receptors. The third specific aim will identify the mechanisms that mediate apoE's anorectic action by determining apoE-relevant receptor(s) and signal transduction pathways. The proposed work is innovative because it assesses a novel physiological function of apoE in the brain. In addition, it takes advantage of the rich research environment in the University of Cincinnati Obesity and Lipid Research Centers and employs available experimental methods and several unique animal models. Moreover, outcomes of this research will have a positive impact on the field of obesity research because the fundamental new knowledge is expected to facilitate the development of preventive and therapeutic interventions to address the epidemic of obesity and, consequently, to decrease health care costs in the United States.

描述（由申请人提供）：载脂蛋白E（APOE）在肝脏和大脑中大量产生。它在脂质的代谢和重新分布中起着重要作用。在大脑中，APOE与发育，再生和神经保护作用有关。最近，我们确定了APOE的新功能，即中央给药的APOE有效地抑制了食物的摄入量和体重，而不会引起毒性的迹象，并阻止内源性脑APOE用其特异性抗体的作用增加食物摄入量。 APOE基因靶向缺失的小鼠比野生型小鼠食用更多的食物并称重更多。这些结果表明，APOE在控制食物摄入和体重的控制中起着至关重要的作用。因此，我们推测不足的APOE产生可能会使一种容易受到肥胖发展的动物。我们的长期目标是确定抑制食欲作为预防和治疗肥胖症的手段的药理目标。该特定应用的目的是确定介导APOE在控制食物摄入和体重的作用的机制。第一个具体目的将评估以下假设：肥胖动物的食物消耗增加部分是由于下丘脑的APOE信号降低，该下丘脑是一种调节能量稳态的中央区域。第二个特定目的将评估下丘脑APOE通过影响分解代谢调节性神经肽和/或其受体发挥其厌食功能的假设。第三个特定目的将通过确定与APOE相关的受体和信号转导途径来识别介导APOE的厌食作用的机制。提出的工作具有创新性，因为它评估了APOE在大脑中的新生理功能。此外，它利用了辛辛那提肥胖大学和脂质研究中心的丰富研究环境，并采用了可用的实验方法和几种独特的动物模型。此外，这项研究的结果将对肥胖研究领域产生积极影响，因为预计新知识将促进预防和治疗干预措施的发展，以解决肥胖症的流行，从而降低美国的医疗保健成本。