TRAPping loss of control in binge eating

导致暴饮暴食失控

基本信息

批准号：
10219019
负责人：
ERIC P ZORRILLA
金额：
$ 26.63万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219019
关键词：
Affective Affinity Chromatography Animal Model Anterior Anxiety Disorders Attention Bariatrics Behavior Behavioral Behavioral Model Binge Eating Binge eating disorder Body Weight decreased Bulimia Clinical Clinical Research Cognitive Data Desire for food Development Eating Eating Disorders Electrophysiology (science)Etiology Exposure to Extinction (Psychology)Food Future Gene Expression Genes Genetic Recombination Goals Human Impairment Impulsivity Insula of Reil Intake Location Measures Mental Depression Mental Health Metabolic syndrome Modeling Molecular Molecular Profiling Neurobiology Neurons Odors Overweight Palate Pathology Population Procedures Process Psychometrics Psychopathology Rattus Research Domain Criteria Resistance Rewards Ribosomes Rodent Role Self Administration Severities Signal Transduction Stimulus Symptoms Testing Translating Viral Weight Gain Work anorexia nervosa binge-purge subtype bariatric surgery behavior measurement biobank cell type cognitive control combinatorial emotion dysregulation experience food addiction genetic approach indexing innovation insight loss of control over eating molecular marker multidisciplinary new therapeutic target novel optogenetics recruit response ribosome profiling social translational study translatome

项目摘要

ABSTRACT Loss of control (LOC) eating, the sense of being unable to control one’s intake, is a hallmark of binge eating and a defining, causal antecedent of binge-type eating disorders1,2. LOC eating also predicts anxiety disorders and depression and, as a core symptom of food addiction is seen in millions of overweight individuals8,12,17-21. Clinically, the severity of LOC eating predicts more eating disorder pathology and emotion dysregulation; impulsivity and impaired inhibitory control; and less weight loss post-bariatric surgery22-30. LOC predicts these measures independent from and more effectively than does the amount eaten28,31-41 and foretells weight gain and metabolic syndrome risk1,2,29,45-51. Recent psychometric finding also suggest that behavioral signs of LOC correlate more with eating disorder pathology and binge eating than do cognitive or affective LOC criteria43. We thus developed a novel model of LOC eating in which rats with intermittent, extended access to palatable food show hallmarks of behavioral LOC in human scales, including increased food-directed effort and intake despite negative consequences, In the present application we will develop the model further to obtain additional, translationally-relevant measures of behavioral LOC (Aim 1). We also will use a sensitive, specific AAV E-SARE to enable neuronal activity-dependent targeted recombination in active populations (TRAP) (Aim 2) in order to dissect a recently identified anterior insula neuronal ensemble implicated in LOC-like eating. The studies will inform the role of intermittent, extended access in the etiology and modeling of behavioral LOC for translational studies. They also will identify the LOC-associated ensemble’s location, molecular markers and causal role. Finally, by leveraging ensemble translatome results with UK Biobank gene association data, the project may identify novel therapeutic targets for LOC eating.

抽象的饮食失控（LOC），即无法控制摄入量的感觉，是暴饮暴食的标志暴饮暴食症的一个明确的因果前因1,2也可以预测焦虑症。抑郁症是食物成瘾的核心症状，在数百万超重个体中可见8,12,17-21。临床上，LOC饮食的严重程度预示着更多的饮食失调病理和情绪失调。冲动和抑制控制受损；以及减肥手术后体重减轻22-30。测量独立于吃的量，并且比吃的量更有效28,31-41，并预示体重增加和代谢综合征风险 1,2,29,45-51 最近的心理测量结果也表明 LOC 的行为迹象。与认知或情感 LOC 标准相比，与饮食失调病理学和暴饮暴食更相关43。因此，我们开发了一种新的 LOC 饮食模型，在该模型中，大鼠间歇性地、长时间地获取可口的食物食物显示出人类行为LOC的特征，包括增加食物导向的努力和摄入量负面后果，在本应用中，尽管我们将进一步开发模型以获得额外的、与转化相关的行为 LOC 测量（目标 1）。 AAV E-SARE 可在活跃群体中实现神经活动依赖性靶向重组 (TRAP)（目标 2）为了解剖最近发现的与LOC样饮食有关的前岛叶神经元群。研究将揭示间歇性、扩展性接触在行为 LOC 的病因学和建模中的作用他们还将确定与 LOC 相关的整体的位置、分子标记和最后，通过利用集成翻译组结果和英国生物银行基因关联数据，该项目可能会确定 LOC 饮食的新治疗靶点。