Adolescent obesity induces sex-specific alterations of action control

The prevalence of obesity is rising worldwide in young people and is associated with poor long-term health outcomes. To counter obesity, weight loss strategies especially involve changes in feeding behaviors and food choice. However, the high level of relapse to unhealthy dietary habits represents an important challenge, suggesting long-term alterations of decision-making and food-seeking processes. Previous studies showed that adolescence is critical for the development of decision-making functions. Thus, it is essential to understand the precise impact of the exposure to obesogenic diets during this life stage on the different processes underlying flexible control of food-seeking actions. To address this, we gave mice access to high-fat diets (HFDs) with different fat contents during adolescence and investigated the long-lasting impact on action control at adulthood after a switch to a healthy diet. We uncovered important sex differences. In both males and females, exposure to HFD with very high-fat content (60%) promote inflexible habitual behavior, which is less flexible to adapt to changes in outcome value or action-outcome relationships. In contrast, exposure to HFD with lower fat content (45%) impaired action control based on the updating of outcome value in males only, while impairing action control based on the updating of action-outcome relationships in females only. These findings highlight how the consumption of obesogenic diets during adolescence has long-lasting, diet- and sex-dependent effects on decision-making processes, promoting habitual responses to food. These changes may support long-term vulnerability for mental and physiological health conditions.