Regulation of Food Intake and Body Weight by Brain Apo E

载脂蛋白E(ApoE)在肝脏和脑中大量产生。它在世界上扮演着重要的角色。 脂类的新陈代谢和再分配。在大脑中，载脂蛋白E与发育、再生、 和神经保护。最近，我们发现了载脂蛋白E的一种新功能，即中枢管理的载脂蛋白E 有效地抑制食物摄入量和体重，而不会引起毒性迹象，并阻止 内源性脑载脂蛋白E及其特异性抗体增加了食物的摄入量。靶向缺失该基因的小鼠 APOE基因比野生型小鼠消耗更多的食物，体重也更重。这些结果表明载脂蛋白E在 在控制食物摄入量和体重方面起着重要作用。因此，我们推测载脂蛋白E不足 生产可能使动物容易患上肥胖症。我们的长期目标是确定 作为预防和治疗肥胖症的手段抑制食欲的药理作用靶点。这个 本研究的目的是明确载脂蛋白E(S)调控载脂蛋白E的作用机制。 食物摄入量和体重。第一个具体目标将评估增加食物的假设 肥胖动物的摄入部分是由于下丘脑的载脂蛋白E信号减少，下丘脑是一个中心区域 调节能量动态平衡。第二个具体目标将评估下丘脑 APOE通过影响分解代谢调节神经肽和/或它们的受体发挥厌食作用。 第三个具体目标将通过确定调节载脂蛋白E厌食作用的机制来确定 载脂蛋白E相关受体(S)及其信号转导途径。拟议的工作具有创新性，因为它 评估了载脂蛋白E在大脑中的一种新的生理功能。此外，它还利用富人的利益 辛辛那提大学肥胖和血脂研究中心的研究环境和员工 可用的实验方法和几种独特的动物模型。此外，本研究的成果 将对肥胖研究领域产生积极影响，因为基本的新知识是 预计将促进制定预防和治疗干预措施，以应对艾滋病的流行 肥胖，从而降低美国的医疗保健成本。

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.