TRAPping loss of control in binge eating

导致暴饮暴食失控

• 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
• 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

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.

摘要 进食失控，即无法控制自己的进食量，是暴饮暴食的标志 以及暴饮暴食型进食障碍的定义性因果前因1，2。暴饮暴食也预示着焦虑症 和抑郁症，作为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，暴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;减肥手术后体重减轻较少22 -30。预测这些 措施独立于和更有效地比吃的量28，31-41，并预示着体重增加 和代谢综合征风险1，2，29，45-51。最近的心理测量发现也表明， 与进食障碍病理学和暴饮暴食的相关性大于认知或情感障碍标准43。 因此，我们开发了一种新的进食模型，在该模型中，大鼠间歇性地， 食物在人类尺度上表现出行为失调的特征，包括增加食物导向的努力和摄入 在本申请中，我们将进一步开发该模型以获得 额外的，预防性相关的行为障碍措施（目标1）。我们还将使用一个敏感的，具体的 AAVE-SARE能够在活性群体中实现神经元活性依赖性靶向重组（TRAP）（Aim 2)为了解剖最近发现的与LOC样进食有关的前额叶神经元系综。的 研究将告知间歇性的作用，延长访问的病因学和建模的行为障碍， 翻译研究他们还将确定与LOC相关的集合的位置，分子标记和 因果作用。最后，通过利用集成翻译组结果与英国生物库基因关联数据， 该项目可能会发现新的治疗目标，为肥胖。