New research from University College Cork shows that voluntary exercise can counteract the mood-damaging impacts of a high-fat, high-sugar diet in rats. The study highlights specific gut metabolites and hormones that explain these benefits. However, poor diet still limits brain neurogenesis despite exercise.
Researchers led by Professor Yvonne Nolan at University College Cork investigated how exercise mitigates the behavioral effects of a Western-style cafeteria diet. Published on October 21, 2025, in the journal Brain Medicine, the study involved adult male rats fed either a standard chow diet or a high-fat, high-sugar cafeteria diet for seven and a half weeks. Half the rats in each group had access to a running wheel to assess voluntary exercise.
The cafeteria diet triggered depression-like behaviors, but running produced an antidepressant-like effect even in those on the unhealthy diet. Metabolomic analysis of caecal contents revealed that the diet altered 100 out of 175 metabolites in sedentary rats. Exercise partially restored balance, particularly boosting three mood-related metabolites: anserine, indole-3-carboxylate, and deoxyinosine, which were reduced by the diet.
Behavioral tests showed the diet alone did not severely impair spatial learning or memory, though exercise slightly enhanced navigation skills and provided mild anti-anxiety effects regardless of diet. Blood analysis indicated elevated insulin and leptin in sedentary cafeteria-fed rats, levels significantly reduced by exercise. Dr. Minke Nota, the study's first author, noted that this hormonal rebalancing may protect against poor diet's behavioral effects.
Exercise increased glucagon-like peptide 1 (GLP-1) in chow-fed rats but weakened this response in cafeteria-fed ones; it boosted peptide YY (PYY) only in the latter group. Fibroblast growth factor 21 (FGF-21) rose with the cafeteria diet irrespective of activity, while glucagon declined.
Notably, the cafeteria diet blocked exercise-induced adult hippocampal neurogenesis, measured by doublecortin-positive cells in the dentate gyrus—a brain area key to emotion and memory. In chow-fed rats, exercise robustly increased neurogenesis.
An editorial by Professor Julio Licinio emphasized, "exercise has an antidepressant-like effect in the wrong dietary context, which is good news for those who have trouble changing their diet." The study, limited to male rats and a seven-week period, suggests exercise aids mood via gut-brain signaling but full neuroplasticity requires good nutrition. Correlations linked gut metabolites like aminoadipic acid and 5-hydroxyindole-3-acetic acid to cognitive performance.