TRAPping loss of control in binge 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 以及暴饮暴食型饮食失调的定义性因果前因1，2。暴饮暴食也预示着焦虑症 和抑郁症，并且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和预示体重增加 和代谢综合征风险1，2，29，45 -51。最近的心理测量发现也表明， 与进食障碍病理学和暴饮暴食的相关性高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。

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.