BEHAVIORAL AND METABOLIC EFFECTS OF PROTEIN-ENRICHED DIETS IN A MOUSE MODEL OF ANOREXIA NERVOSA-LIKE FOOD RESTRICTION

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by self-imposed food restriction, excessive physical activity, and paradoxical metabolic adaptations despite profound weight loss. Clinical observations indicate that patients with AN often avoid high-calorie foods and preferentially consume protein-enriched diets, suggesting a coping strategy to regulate hunger, glycemia, and anxiety. Here, we investigated behavioral and metabolic impact of a protein-enriched diet (PED) in an AN-like mouse model combining food restriction (FR) and voluntary physical activity. Female C57BL/6J mice (n=8/group) were assigned to eight experimental groups according to feeding condition (ad libitum or FR), access to a running wheel, and diet composition (standard: 16%, or PED: 51% protein) over 20 days. Food intake, body weight, glycemia, and locomotor activity were monitored, followed by anxiety-like behavioral assessments and food preference test. PED exposure reduced food intake and body weight in ad libitum mice and lowered basal glycemia across feeding conditions. Diet history differentially shaped behavioral outcomes: ad libitummice exposed to PED displayed reduced PED preference, whereas FR mice with wheel access showed a shift in nocturnal activity and heightened initial exploration in the open field. Across conditions, PED exposure was associated with a partial reduction in anxiety-like behaviors. These findings suggest that PED modulates both metabolic regulation and behavioral responses in an AN-like context and may represent a compensatory mechanism to cope with energy deficit and anxiety. Ongoing work aims to identify the underlying neurobiological substrates, with a focus on striatum–amygdala and hypothalamic circuits involved in emotional and metabolic regulation.