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：
7337061
负责人：
Min Liu
金额：
$ 28.21万
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/7337061
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

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.

载脂蛋白E（APOE）在肝脏和大脑中大量产生。它在代谢和脂质的重新分布。在大脑中，ApoE与发展，再生有关，和神经保护。最近，我们确定了APOE的新功能，即中央管理的ApoE 有力地抑制食物的摄入量和体重，而不会引起毒性迹象，并阻止内源性脑APOE及其特异性抗体会增加食物摄入量。有针对性删除的小鼠 Apoe基因消耗更多的食物并比野生型小鼠体重更多。这些结果暗示着Apoe的播放在控制食物摄入和体重的控制中起着重要作用。因此，我们推测APOE不足生产可能会使一种容易发育的动物。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靶标。这该特定应用的目的是确定介导APOE在控制中的作用的机制食物摄入和体重。第一个具体目的将评估增加食物的假设肥胖动物的消费部分是由于下丘脑的APOE信号降低，这是一个中心区域调节能量稳态。第二个特定目的将评估下丘脑的假设 ApoE通过影响分解代谢的神经肽和/或其受体发挥其厌食功能。第三个特定目的将通过确定介导APOE的厌食作用的机制与APOE相关的受体和信号转导途径。拟议的工作是创新的，因为它评估APOE在大脑中的新生理功能。此外，它利用了富人辛辛那提肥胖和脂质研究中心的研究环境可用的实验方法和几种独特的动物模型。而且，这项研究的结果将对肥胖研究领域产生积极影响，因为新知识的基本知识是有望促进预防和治疗干预措施的发展，以解决肥胖，因此，在美国降低医疗保健成本。