The role of brain mu-opioid receptor and food environment in the development of obesity

脑μ阿片受体和食物环境在肥胖发生中的作用

• 批准号: 8832373
• 负责人: Candace M Reno
• 金额: $ 4.89万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-24 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832373
• 关键词: Affect; Automobile Driving; Body Weight; Brain; Brain region; Calories; Cardiovascular Diseases; Development; Diabetes Mellitus; Diet; Disease; Dopamine; Eating; Environment; Epidemic; Fatty acid glycerol esters; Feeding behaviors; Feeling; Food; Genetic Predisposition to Disease; Health; Hunger; Individual; Lead; Malignant Neoplasms; Mediating; Modeling; Neurons; Obesity; Opioid Receptor; Pathway interactions; Persons; Phenotype; Play; Rattus; Regulation; Research; Resistance; Rewards; Role; Satiation; Signal Transduction; Site; Testing; Therapeutic; Ventral Tegmental Area; brain metabolism; brain pathway; combat; feeding; food environment; gamma-Aminobutyric Acid; insight; mesolimbic system; mind control; mu opioid receptors; neural circuit; novel therapeutic intervention; optogenetics; overexpression; research study; restoration; satisfaction; sugar

DESCRIPTION (provided by applicant): Obesity has reached epidemic proportions worldwide. An understanding of why this epidemic has occurred is essential for therapeutic treatments to be developed. The availability of foods high in fat and sugar is thought to play a major role in th obesity epidemic. The brain controls feeding behavior by driving the want to eat these foods that are high in calories. The brain normally perceives signals of fullness or hunger which in turn tell a person to stop or start eating, respectively. These signals are thought to be disrupted in obesity. The proposed research aims to understand the brain circuits involved in feeding regulation and how these circuits are disrupted in obesity. This research utilizes a rat model in which rats are either genetically predisposed to become obese or not. When these rats are placed on high fat diets, they either become obese (obese prone) or remain lean (obese resistant). These obese prone rats have disruption in critical brain pathways involved in feeding regulation that leads to overconsumption of high fat foods and, ultimately, obesity. Specifically, the μ-opioid receptor is elevated in the brain of obese rats and may lead to disruption in pathways involved in food reward and satiety. Manipulation of μ-opioid receptor through knockdown or overexpression within these brain regions will be done to understand how food choice and body weight are disrupted. Furthermore, neurons within brain regions involved in food reward will be activated or inhibited to identify how these neuronal circuits regulate a choice between normal food and high fat food. Results from these experiments will deepen our understanding of how the brain perceives fullness and the desire to eat high fat and high sugar foods and how to correct the disruption that occurs in obesity.

描述（由申请人提供）：肥胖已达到全球流行病的比例。了解这种流行病发生的原因对于开发治疗方法至关重要。人们认为高脂肪和高糖食物的供应在肥胖症的流行中起着重要作用。大脑通过驱动进食这些高热量食物的欲望来控制进食行为。大脑通常会感知饱腹或饥饿的信号， 一个人停止或开始吃，分别。这些信号被认为在肥胖症中被破坏。这项拟议中的研究旨在了解参与进食调节的大脑回路，以及这些回路在肥胖症中是如何被破坏的。这项研究利用了一种大鼠模型，在这种模型中，大鼠要么有肥胖的遗传倾向，要么没有。当这些大鼠被置于高脂肪饮食中时，它们要么变得肥胖（肥胖倾向），要么保持瘦（肥胖抵抗）。这些肥胖倾向的大鼠在参与进食调节的关键大脑通路中受到破坏，导致过度食用高脂肪食物，最终导致肥胖。具体来说，肥胖大鼠大脑中的μ-阿片受体升高，可能导致与食物奖励和饱腹感有关的通路中断。通过在这些大脑区域内敲低或过表达来操纵μ-阿片受体，以了解食物选择和体重是如何被破坏的。此外，参与食物奖励的大脑区域内的神经元将被激活或抑制，以确定这些神经元回路如何调节正常食物和高脂肪食物之间的选择。这些实验的结果将加深我们对大脑如何感知饱腹感和吃高脂肪和高糖食物的欲望以及如何纠正肥胖中发生的中断的理解。