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 失去控制（LOC）进食，无法控制自己的摄入量的感觉，是暴饮暴食的标志 还有一个定义的，因果关系饮食失调的先例1,2。 LOC饮食还可以预测焦虑症 抑郁症以及作为食物成瘾的核心症状，有数百万超重的人8,12,17-21。 在临床上，LOC饮食预测的严重程度更多的饮食失调病理和情绪失调； 冲动性和抑制性控制受损；减少体重后手术后22-30。 LOC预测这些 与食用的28,31-41相比，措施独立于和更有效的措施，预测体重增加 和代谢综合征风险1,2,29,45-51。最近的心理测量发现还表明LOC的行为迹象 与认知或情感LOC标准43相比，与饮食失调病理和暴饮暴食的相关性更多。 因此，我们开发了一种新型的LoC饮食模型，其中大鼠间歇性，扩展可口的途径 食品展览的标志是人类量表的行为LOC，包括增加的努力和摄入量 尽管后果负面后果，但在演示应用中，我们将进一步开发该模型以获得 行为LOC的其他相关，相关的测量（AIM 1）。我们还将使用敏感的，特定的 AAV电子护理可以使神经元活动依赖于活性种群的靶向重组（陷阱）（AIM 2）为了剖析最近鉴定出的与LOC样饮食有关的前岛神经元合奏。这 研究将告知间歇性，扩展访问在病因和行为LOC的建模中的作用 翻译研究。他们还将确定与LOC相关的合奏的位置，分子标记和 因果角色。最后，通过利用英国生物库基因关联数据的合奏转换结果， 项目可能会确定新型的LOC饮食靶标。

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