ESPE Abstracts

Anorexia nervosa (AN) is a multifaceted and debilitating illness characterized by self-induced starvation, persistent anxiety about weight gain, preoccupation with body image, and maladaptive food choices. It is characterized by the disruption in homeostatic energy balance mechanisms and the persistence of homeostatic hunger is overridden by dysfunctional self-regulatory and reward pathways that drive food aversion and severely restrict food intake. Epidemiological studies have consistently shown that (AN) has a higher incidence among females than males. Starvation is associated with elevated activity of hypothalamic neurons that produce AgRP, which cells are crucial for feeding and controlling compulsive exercise and survival in the activity-based anorexia model (ABA). Here, we interrogated whether these hypothalamic neurons mediate sex differences during the ABA paradigm. Using a combined pharmacologic and genetic approach, we found that when AgRP neurons are ablated, male mice exhibited higher food intake, lower body weight loss, and decreased physical activity during the food intake and the post-prandial period compared to age-matched female mice. Our results suggest that when AgRP neurons are ablated, male mice are less prone to develop AN and shed new light on sex differences in fundamental homeostatic neural circuits.