TRAPping loss of control in binge eating

摘要 失控进食(LOC)，即无法控制摄入量的感觉，是暴食的标志 暴饮型进食障碍的一个明确的因果前置因素1，2.进食LOC也预示着焦虑症 和抑郁，作为食物成瘾的核心症状，数百万超重者8，12，17-21岁。 在临床上，进食LOC的严重程度预示着更多的进食障碍病理和情绪失调； 冲动和抑制控制受损；减肥手术后体重减轻22-30岁。LoC预测到了这些 独立于并比28，31-41的进食量更有效地测量并预测体重增加 代谢综合征风险1，2，29，45-51。最近的心理测量学发现也表明，LOC的行为迹象 与认知或情感LOC标准43相比，进食障碍、病理和暴饮暴食的相关性更大。 因此，我们开发了一种新的LOC进食模型，在该模型中，大鼠断断续续地、延长了对可口食物的接触 食物在人体尺度上显示出行为LOC的特征，包括食物导向的努力和摄入量增加 尽管有负面后果，但在本应用程序中，我们将进一步开发模型以获得 另外，与翻译相关的行为LOC衡量标准(目标1)。我们还将使用敏感、具体的 AAV E-sARE使活跃人群中神经元活性依赖的靶向重组(TRAP)(AIM 2)为了解剖最近发现的与LOC样进食有关的前岛神经元群。这个 研究将告知间歇性、延长通路在行为LOC的病因学和模型化中的作用 翻译研究。他们还将确定与LOC相关的群体的位置、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整体翻译组结果， 该项目可能会为食用低碳水化合物确定新的治疗靶点。

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.