TRAPping loss of control in binge eating

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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.