Neurochemical mechanisms of bingeing on palatable foods

暴饮暴食可口食物的神经化学机制

• 批准号: 7329047
• 负责人: NICOLE M AVENA
• 金额: $ 4.68万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329047
• 关键词: Acetylcholine; Affect; Amino Acids; Animal Model; Appetitive Behavior; Area; Arousal; Basic Science; Behavior; Behavior Disorders; Behavioral; Binge Eating; Biochemical; Biological Assay; Biological Process; Blood; Brain; Brain region; Canned Foods; Capillary Electrophoresis; Characteristics; Clinical; Collection; Consult; Consumption; Developed Countries; Diet; Dietary Fats; Dopamine; Drug Addiction; Drug usage; Eating Behavior; Eating Disorders; Endocrine; Endocrine System Diseases; Enkephalins; Etiology; Fatty acid glycerol esters; Feeding Patterns; Feeding behaviors; Food; Glutamates; Goals; Hypothalamic structure; Immunohistochemistry; In Situ Hybridization; Incidence; Intake; Knowledge; Laboratories; Lateral; Learning; Lipids; Macronutrients Nutrition; Measurement; Measures; Messenger RNA; Microdialysis; Mission; Molecular; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Mental Health; Neurons; Neurotransmitters; Nucleus Accumbens; Obesity; Opioid; Opioid Peptide; Peptides; Personal Satisfaction; Pharmaceutical Preparations; Population; Procedures; Process; Property; Prosencephalon; Public Health; Radioimmunoassay; Rattus; Research; Research Personnel; Resources; Rewards; Role; Satiation; Schedule; Steroids; Supervision; Techniques; Testing; Training; Universities; Work; brain behavior; clinically relevant; design; drug of abuse; experience; extracellular; feeding; gamma-Aminobutyric Acid; hypocretin; in vivo; mRNA Expression; metabolic abnormality assessment; neurochemistry; neuromechanism; novel; relating to nervous system; response; steroid hormone; sugar

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.

描述（由申请人提供）：肥胖目前对工业化国家的公共健康构成威胁，因此与 NIMH 通过研究大脑和行为来减轻行为障碍负担的使命直接相关。这也与 NIDDK 的使命相关，即利用基础科学研究影响公共健康的代谢和内分泌疾病。暴食可口食物是肥胖和其他饮食失调的行为特征，这使得了解其行为背后的神经机制具有重大的临床意义和至关重要的意义。暴饮暴食可口的食物会引起大脑的行为和改变，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。本提案的主要目标是让我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技术来识别和表征暴食可口食物和药物滥用背后的一些常见神经机制。该提案将测量调节进食行为和药物依赖性的大脑区域（即外侧下丘脑（LH）和伏隔核（NAc））中阿片类和非阿片类肽的表达以及氨基酸释放。这些分析将根据暴食可口食物（脂肪与糖）与随意获取食物的情况进行比较。此外，还将收集类固醇激素和脂质循环水平的测量值，并将其与大脑中的这些神经化学变化相关联。我建议测试以下新假设：1) LH 中的阿片类药物和氨基酸与可口食物的常量营养素含量相关，与获取时间表无关，而在 NAc 中，它们的功能与间歇性获取导致的暴饮暴食有关美味的食物； 2) 这些大脑区域及其各自的功能通过 LH 中投射到 NAc 的非阿片类、促食欲肽神经元群连接； 3) 循环中的类固醇和脂质因食用可口的高脂肪饮食而升高，它们调节 LH 和 NAc 的神经化学物质，从而促进暴饮暴食富含脂肪的食物。这项研究将确定与肥胖相关的暴食背后的一些神经和分子机制，这是一个重要的公共卫生问题。关于暴食富含脂肪食物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。