Neurochemical mechanisms of bingeing on palatable foods

描述(申请人提供)：肥胖目前对工业化国家的公共健康构成威胁，因此与NIMH通过对大脑和行为的研究来减少行为障碍的负担的使命直接相关。这也与NIDDK利用基础科学研究影响公共健康的代谢和内分泌疾病的使命有关。暴饮暴食是肥胖和其他饮食障碍的一种行为特征，因此了解其行为的神经机制具有重要的临床意义和极其重要的意义。暴饮暴食会导致大脑中的行为和变化，类似于滥用药物的影响；然而，人们对这种现象背后的神经化学或分子机制知之甚少。这项建议的主要目的是学习和应用原位杂交、免疫组织化学、放射免疫分析和毛细管电泳法等技术，以识别和表征一些常见的神经机制，这些机制导致暴饮暴食和药物使用。这项建议将测量阿片和非阿片肽的表达以及大脑中调节摄食行为和药物依赖的区域，即下丘脑外侧核(LH)和伏核(NAC)的氨基酸释放。这些分析将作为暴饮暴食(脂肪与糖)与随意获取食物的函数进行比较。此外，还将收集与大脑中这些神经化学变化相关的类固醇激素和脂质循环水平的测量结果。我建议测试新的假说：1)类阿片和氨基酸在促黄体生成素中的功能与美味食物的大量营养素含量无关，而在新的促肾上腺皮质中，它们的功能与因间歇接触美味食物而导致的暴饮暴食有关；2)这些大脑区域及其各自的功能通过促黄体生成素的非阿片类、促食氧肽神经元群投射到新的促进器而联系在一起；3)循环中的类固醇和类脂，通过食用美味的高脂肪饮食而增加，调节促黄体生成素和促肾上腺皮质激素的神经化学物质，从而促进暴饮暴食高脂肪食物的过程。这项研究将确定暴饮暴食与肥胖相关的一些神经和分子机制，肥胖是一个重要的公共健康问题。有关暴饮暴食的大脑过程的信息将有助于开发治疗方法，以减少这种行为，并最终减少肥胖的发生率。

DESCRIPTION (provided by applicant): Obesity currently poses a threat to public health in the industrialized nations and therefore is directly relevant to the mission of the NIMH to reduce the burden of behavioral disorders through research on the brain and behavior. It is also relevant to the mission of the NIDDK to study metabolic and endocrine disorders affecting public health using basic science. Binge eating of palatable foods is a behavioral characteristic of obesity and other eating disorders, making it of great clinical relevance and utmost importance to understand neural mechanisms underlying its behavior. Bingeing on palatable foods can induce behaviors and alterations in the brain that are similar to the effects of drugs of abuse; however, little is known about the neurochemical or molecular mechanisms underlying this phenomenon. The primary goal of this proposal is for me to learn and apply the techniques of in situ hybridization, immunohistochemistry, radioimmuno-assay and capillary electrophoresis to identify and characterize some common neural mechanisms underlying binge eating of palatable foods and drug use. This proposal will measure opioid and non-opioid peptide expression as well as amino acid release in areas of the brain that regulate both feeding behavior and drug dependence, namely, the lateral hypothalamus (LH) and nucleus accumbens (NAc). These analyses will be performed as a function of binge eating of palatable foods (fat vs. sugar) compared with ad libitum access to the food. In addition, measures of circulating levels of steroid hormones and lipids will be collected and related to these neurochemical changes in the brain. I propose to test the novel hypotheses that: 1) opioids and amino acids in the LH function in relation to the macronutrient content of a palatable food independent of access schedule, whereas in the NAc they function in relation to the binge eating resulting from intermittent access to a palatable food; 2) these brain regions and their respective functions are connected via a population of non-opioid, orexigenic peptide neurons in the LH that project to the NAc; 3) the circulating steroids and lipids, which are elevated by consumption of a palatable, high-fat diet, modulate the neurochemicals of the LH and NAc that contribute to the process of binge eating of fat- rich foods. This research will identify some neural and molecular mechanisms underlying binge eating associated with obesity, which is an important public health issue. Information about the processes in the brain underlying binge eating of fat-rich foods will be useful for developing treatments to reduce this behavior and ultimately the incidence of obesity.