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Vulnerability and Resilience to Activity-Based Anorexia is Not Sex-Dependent

Zhao, J.; Beeler, J. A.; Burghardt, N. S.

2026-06-10 neuroscience
10.64898/2026.06.05.730470 bioRxiv
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IntroductionAnorexia nervosa (AN) is more prevalent in women than men, although rates in men are rising. Animal models can provide insight into whether this differential prevalence is rooted in biological mechanisms, but prior studies have yielded conflicting findings. Using the activity-based anorexia (ABA) model, we previously demonstrated that female mice exhibit distinct vulnerable and resilient phenotypes. Here, we use this phenotypic framework to investigate sex differences in ABA susceptibility. MethodsWe tested young adult male C57BL/6N mice using the same ABA protocol used to test age-matched C57BL/6N females. Individual differences in daily bodyweight, food intake, water intake, and wheel running were analyzed and compared across sexes. ResultsMales exhibit the same vulnerable and resilient phenotypes as females, with no sex difference in the proportion of mice exhibiting each phenotype or the repertoire of behaviors characterizing them. In both sexes, vulnerable mice exhibit catastrophic weight loss driven by excessive light cycle running, while resilient mice exhibit weight stabilization driven by adaptive changes in consumption. Running during the feeding window revealed that vulnerability is not driven by a decision to run instead of eat in either sex. ConclusionsABA models adaptive and maladaptive responses to food restriction in both sexes. Behavioral responses to starvation are similar across sexes, suggesting that sex differences in AN prevalence may be driven by stronger sociocultural pressures faced by women to lose weight.

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