Weight loss after obesity disrupts cognitive flexibility through reinforcement learning strategies
Author(s)
Type
Journal Article
Abstract
Objective
Despite successful weight loss, many individuals with obesity regain weight, yet cognitive factors in the weight loss state remain unclear. Here, we tested whether obesity induces deficits in cognitive flexibility, a core component of reinforcement learning (RL), after body weight normalizes.
Methods
Male and female C57BL/6J mice were exposed to high-fat diet-induced obesity followed by weight loss. Weight loss and control mice were tested on a modified probabilistic reversal learning (PRL) task to assess cognitive flexibility and a progressive-ratio (PR) task to evaluate motivation. RL modeling was applied to dissociate latent decision-making parameters.
Results
Post-weight-loss mice exhibited persistent impairments in PRL efficiency. Males showed reduced late-phase reversal efficiency (p < 0.001), while females showed early-phase inefficiency but later recovery (p < 0.05). RL modeling revealed reduced learning rates in both sexes, indicating impaired value updating despite intact motivation, as PR performance did not differ between groups. Across tasks, food intake remained unchanged, suggesting reduced efficiency reflected cognitive inflexibility rather than diminished appetite.
Conclusions
Weight loss after obesity produced sex-specific RL deficits. These findings dissociated motivational drive from cognitive flexibility and highlighted maladaptive decision-making as a feature of the weight loss state. This demonstrates the need for targeted interventions addressing post-weight-loss cognitive barriers.
Despite successful weight loss, many individuals with obesity regain weight, yet cognitive factors in the weight loss state remain unclear. Here, we tested whether obesity induces deficits in cognitive flexibility, a core component of reinforcement learning (RL), after body weight normalizes.
Methods
Male and female C57BL/6J mice were exposed to high-fat diet-induced obesity followed by weight loss. Weight loss and control mice were tested on a modified probabilistic reversal learning (PRL) task to assess cognitive flexibility and a progressive-ratio (PR) task to evaluate motivation. RL modeling was applied to dissociate latent decision-making parameters.
Results
Post-weight-loss mice exhibited persistent impairments in PRL efficiency. Males showed reduced late-phase reversal efficiency (p < 0.001), while females showed early-phase inefficiency but later recovery (p < 0.05). RL modeling revealed reduced learning rates in both sexes, indicating impaired value updating despite intact motivation, as PR performance did not differ between groups. Across tasks, food intake remained unchanged, suggesting reduced efficiency reflected cognitive inflexibility rather than diminished appetite.
Conclusions
Weight loss after obesity produced sex-specific RL deficits. These findings dissociated motivational drive from cognitive flexibility and highlighted maladaptive decision-making as a feature of the weight loss state. This demonstrates the need for targeted interventions addressing post-weight-loss cognitive barriers.
Date Issued
2026-01-01
Date Acceptance
2025-08-25
Citation
Obesity, 2026, 34 (1), pp.188-198
ISSN
1930-7381
Publisher
Wiley
Start Page
188
End Page
198
Journal / Book Title
Obesity
Volume
34
Issue
1
Copyright Statement
© 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41152694
Publication Status
Published
Coverage Spatial
United States
Article Number
oby.70057
Date Publish Online
2025-10-28