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）：肥胖症目前对工业化国家的公共卫生构成威胁，因此与NIMH的使命直接相关，以减轻对大脑和行为的研究来减轻行为障碍的负担。这也与NIDDK的使命有关使用基础科学研究影响公共卫生的代谢和内分泌疾病的使命。饮食可口食品是肥胖症和其他饮食失调的行为特征，使其具有很大的临床相关性，并且最重要的是了解其行为的神经机制。对可口食品的暴饮暴食可以引起大脑的行为和改变，这与滥用药物的影响相似。然而，关于这种现象的基础的神经化学或分子机制知之甚少。该提案的主要目的是让我学习和应用原位杂交，免疫组织化学，放射膜弥纪和毛细血管电泳的技术，以识别和表征一些暴饮暴食的饮食饮食和药物使用的常见神经机制。该建议将在大脑区域中测量阿片类药物和非阿片类肽的表达以及氨基酸的释放，这些区域调节喂养行为和药物依赖性，即下丘脑（LH）和副胞核（NAC）（NAC）。这些分析将作为对食物的狂饮（脂肪与糖）的暴饮暴食（脂肪与糖）的函数进行。此外，将收集类固醇激素和脂质水平的测量，并与大脑中的这些神经化学变化有关。我建议测试：1）LH功能中的阿片类药物和氨基酸，相对于可口食品的大量营养素含量，而与访问时间表无关，而在NAC中，它们与狂饮饮食相关的作用是由间歇性地进入可口的食物而引起的。 2）这些大脑区域及其各自的功能是通过LH中NAC的LH中非阿片类药物神经元的种群进行的； 3）循环类固醇和脂质通过食用可口的高脂饮食而升高，调节LH和NAC的神经化学物质，这有助于散发富含脂肪的食物的过程。这项研究将确定与肥胖相关的暴饮暴食性饮食中的一些神经和分子机制，这是一个重要的公共卫生问题。关于富含脂肪的食物的大脑过程中的过程的信息对于开发治疗以减少这种行为并最终导致肥胖症的发生率很有用。