TRAPping loss of control in binge eating

导致暴饮暴食失控

• 批准号: 10397637
• 负责人: ERIC P ZORRILLA
• 金额: $ 22.19万
• 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 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397637
• 关键词: Affective; Affinity Chromatography; Animal Model; Animals; Anterior; Anxiety Disorders; Attention; 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; Individual; Insula of Reil; Intake; Location; Measures; Mental Depression; Mental Health; Metabolic syndrome; Modeling; Molecular; Molecular Profiling; Neurobiology; Neurons; Odors; Overweight; Palate; Pathology; Patients; Population; Procedures; Process; Psychometrics; Psychopathology; Rattus; Research Domain Criteria; Resistance; Rewards; Ribosomes; Risk; Rodent; Role; Self Administration; Severities; Signal Transduction; Stimulus; Symptoms; Testing; Translating; Viral; Weight Gain; Woman; 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 disorders 1,2. LOC eating also predicts anxiety disorders and depression and, as a core symptom of food addiction is seen in millions of overweight individuals 8,12,17-21. 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 surgery 22-30. LOC predicts these measures independent from and more effectively than does the amount eaten 28,31-41 and foretells weight gain and metabolic syndrome risk 1,2,29,45-51. 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 criteria 43. 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 以及暴饮暴食型饮食失调的明确因果前因1,2。 LOC饮食也可以预测焦虑症 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；减肥手术后体重减轻较少 22-30。 LOC预测这些 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还表明，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的相关性更大 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 尽管有负面后果，在本应用中，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）。我们还将使用敏感的、特定的 AAV E-SARE 可在活跃群体中实现神经元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。这 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 转化研究。他们还将确定与 LOC 相关的整体的位置、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。

项目成果

Converging vulnerability factors for compulsive food and drug use.

• DOI: 10.1016/j.neuropharm.2021.108556
• 发表时间: 2021-09-15
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Serafine KM;O'Dell LE;Zorrilla EP
• 通讯作者: Zorrilla EP

Decreased excitability of leptin-sensitive anterior insula pyramidal neurons in a rat model of compulsive food demand.

• DOI: 10.1016/j.neuropharm.2022.108980
• 发表时间: 2022-05-01
• 期刊: NEUROPHARMACOLOGY
• 影响因子: 4.7
• 作者: Kirson, Dean;Bagsic, Samantha R. Spierling;Murphy, Jiayuan;Chang, Hang;Vlkolinsky, Roman N.;Pucci, Sarah;Prinzi, Julia A.;Williams, Casey Y.;Fang, Savannah;Roberto, Marisa P.;Zorrilla, Eric
• 通讯作者: Zorrilla, Eric