The role of mu opoid receptors in diet-induced obesity

描述（由申请人提供）： 肥胖是北美最常见的营养失调症;当能量摄入大于能量消耗时，它就会发展。饮食中的脂肪水平，以及份量大小，被认为在促进肥胖的个体数量方面起着重要作用。这强调了需要了解不仅调节食物摄入量而且调节对脂肪的高度偏好的因素。在大量影响食物摄入的肽、神经递质和受体中，只有少数被证明会使动物吃得过多，增加它们对脂肪的偏好。该列表中包括μ阿片受体。μ阿片受体使动物暴饮暴食并增加对高脂肪饮食的偏好的确切机制尚不清楚。我们所知道的是，在肥胖动物中，这种受体数量在中枢神经系统的多个区域显着增加，这些区域已知与进食行为有关。我们假设增加的μ阿片受体有助于在肥胖动物中观察到的暴饮暴食和增加的脂肪偏好。本申请的目的是确定1）是什么导致μ阿片受体在肥胖动物中增加; 2）μ阿片受体使动物[原文如此]过度吞噬并增加脂肪偏好的潜在机制; 3）增加的μ阿片受体是否促进肥胖的发展。从研究中获得的结果可以提供一个潜在的目标，以减轻在肥胖人群中观察到的暴饮暴食和增加的脂肪偏好[原文如此]。我们的研究计划将采用多学科方法，让K 01职业发展奖的候选人在测试中心假设的同时学习几种技术。研究计划的各个方面将在彭宁顿生物医学研究中心（巴吞鲁日，LA）进行。申办者（乔治A.布雷）和共同赞助商（博士伊丽莎白弗洛伊德，格琳达赫尔曼和理查德罗杰斯）随着一个高度互动的基础和临床研究环境，沿着，将为候选人提供一个很好的培训机会，以促进她过渡到成为一个成功的独立研究者。 公共卫生相关性：肥胖症每年造成大约10万至30万人死亡，使这种疾病成为美国仅次于吸烟的第二大死亡原因。这项应用将为肥胖的原因提供新的见解，并提供一个目标，以帮助减轻这种疾病的发展。

DESCRIPTION (provided by applicant): Obesity is the most common nutritional disorder in North America; it develops when energy intake is greater than energy expenditure. The level of fat in the diet, together with portion size, is thought to play a major role in promoting the number of individuals who are obese. This emphasizes the need to understand the factors that are involved in modulating not only food intake but also the high preference for fat. Of the large number of peptides, neurotransmitters, and receptor populations that affect food intake, only a few have been demonstrated to make animals overeat and increase their fat preference. Included in this list are mu opioid receptors. The precise mechanism(s) by which mu opioid receptors make animals overeat and increase the preference for a high fat diet is unknown. What is know [sic] is that in obese animals, this receptor population is significantly increased in multiple areas of the central nervous system that are known to be involved in feeding behavior. We hypothesize that the increased mu opioid receptors are contributing to the overeating and increased fat preference that is observed in obese animals. The goals of this application are to determine 1)what causes mu opioid receptors to increase in obese animals; 2)potential mechanisms by which mu opioid receptors make aniamls [sic] hyperphagic and increase fat preference; 3)if increased mu opioid receptors potentiates the development of obesity. The results obtained from the studies can provide a potential target to attenuate the overeating and increased fat prefrence [sic] that is observed in humans that are obese. Our research plan will use a multi-disciplinary approach to allow the candiate [sic] of this K01 career development award to learn several techniques while testing the central hypothesis. Each aspect of the research plan will be conducted at Pennington Biomedical Research Center (Baton Rouge, LA). The sponsor (Dr. George A. Bray) and co-sponsors (Drs. Elizabeth Floyd, Gerlinda Hermann and Richard Rogers) along with a highly interactive basic and clinical research environment, will offer the candidate a great training opportunity to facilitate her transition into becoming a successful independent investigator. PUBLIC HEALTH RELEVANCE: Obesity accounts for approximately 100,000 to 300,000 deaths a year, making this disease the second-leading cause of death in the United States second only to smoking. This application will provide new insights into the cause of obesity and provide a target to help alleviate the development of this disease.