Running repairs what junk food breaks down in the brain

To investigate this, the team studied adult male mice that were fed either a standard diet or a rotating cafeteria diet consisting of foods high in fat and sugar for seven and a half weeks. Half of the animals in each group were given access to a running wheel. This setup allowed the researchers to distinguish between the separate and combined effects of diet quality and physical activity on the brain and behavior.

New mechanisms linking exercise and mood

The results showed that voluntary running produced an antidepressant-like effect even when the mice ate an unhealthy diet, suggesting that regular physical activity could benefit people who eat Western-style foods.

Using a comprehensive metabolic approach, Professor Nolan and her colleagues examined the cecal contents of animals and found that the cafeteria diet profoundly changed gut metabolism. Of the 175 metabolites analyzed in sedentary mice, 100 were significantly affected. Exercise affected a smaller subset of these, partially restoring balance. Three metabolites known to play a role in mood regulation — anserin, indole-3-carboxylate, and deoxyinosine — were reduced by the cafeteria diet but rebounded with exercise.

Behavioral tests that assess learning, memory and emotional responses revealed further insights. The cafeteria diet alone did not significantly impair spatial learning or recognition memory, but it did exercise slightly improved navigational skills. Researchers also found mild anti-anxiety effects of exercise regardless of diet type.

What are the contents of the cecum?

the term Cecal contents Refers to the materials contained within The blind manA cyst located at the beginning of the large intestine. In animals such as mice, this area is rich in gut microbes that help break down food and produce a wide range of chemical compounds called metabolites. Scientists often analyze cecal contents to understand how diet, exercise, or medications affect gut health and metabolism.

Hormonal pathways in the relationship between diet and exercise

Analysis of blood samples revealed strong hormonal changes that reflected the behavioral results. Sedentary mice who followed the cafeteria diet had sharply higher levels of insulin and leptin, but these elevations were significantly reduced in those who exercised. According to Dr. Minke Nauta, first author of the study, hormonal rebalancing may help explain how exercise protects against the behavioral effects of a poor diet.

The team also identified complex interactions between diet and exercise that involve other hormones that regulate metabolism. In animals on regular chow, exercise boosted glucagon-like peptide 1 (GLP-1) levels, but this response was blunted in those on the cafeteria diet. In contrast, exercise increased peptide YY (PYY) levels only in cafeteria-fed mice, suggesting that compensatory hormonal mechanisms help stabilize metabolism when diet quality is low.

Fibroblast growth factor 21 (FGF-21) levels increased significantly in response to the cafeteria diet regardless of physical activity, whereas glucagon levels decreased. Together, these findings reveal a complex hormonal network through which diet and exercise interact to influence metabolism and brain function.

Implications for understanding relationships between diet and the brain

Perhaps most interesting, the study found that the cafeteria diet prevented the typical exercise-induced increase in adult hippocampal neurogenesis (the formation of new neurons), as measured by double cortin-positive cells in the dentate gyrus. In animals fed regular chow, exercise led to a strong increase in neurogenesis throughout the hippocampus, an area of ​​the brain involved in emotion and memory. This finding suggests that diet quality may fundamentally alter the brain’s ability to benefit from physical activity at the cellular level.

The research team conducted correlation analyzes to determine relationships between specific metabolites and behavioral outcomes. Several cecal metabolites, including aminodipic acid and 5-hydroxyindole-3-acetic acid, have shown negative associations with cognitive performance. These associations were independent of experimental condition, suggesting fundamental relationships between gut metabolite profiles and brain function.

An accompanying editorial by Professor Julio Licinio and colleagues emphasizes the clinical importance of these findings, noting that “exercise has an antidepressant effect in the wrong nutritional context, which is good news for those who find it difficult to change their diet.” The editorial highlights how this research provides a biological framework for understanding why exercise remains beneficial even when nutritional improvements are difficult to implement.

Future directions and clinical translation

The study raises important questions about the optimal sequence of lifestyle interventions. The findings suggest that while exercise can provide mood benefits regardless of diet quality, achieving full neuroplasticity benefits may require attention to nutritional status. This has implications for the design of interventions that increase feasibility and biological impact.

Several limitations are worth considering. The study was conducted exclusively in male rats, and sex differences in metabolic and neural responses to diet and exercise are well documented. In addition, the seven-week intervention period may not be able to capture long-term adaptations that can arise with chronic exposure. Future studies including female animals, longer intervention periods, and dose-response designs will help improve understanding of these complex interactions.

The research also opens new ways to study specific metabolites as potential therapeutic targets. The protective effects of exercise on levels of anserine, indole-3-carboxylate, and deoxynosine suggest that these compounds may serve as biomarkers or even therapeutic agents for mood disorders. The strong associations between specific gut metabolites and behavioral measures support a growing interest in the gut-brain axis as a target for mental health interventions.

This peer-reviewed research represents a major advance in understanding the biological mechanisms linking diet, exercise, and mental health, and provides new insights into how lifestyle factors interact at the molecular and cellular levels to influence brain function. The findings challenge existing models about the relationship between metabolic health and mental health by showing that exercise can provide antidepressant-like effects even in the context of poor dietary choices. By using innovative metabolomics methods combined with comprehensive behavioral and neurobiological assessments, the research team has generated data that not only advances fundamental knowledge, but also suggests practical applications for addressing mental health challenges associated with modern dietary patterns. The reproducibility and validation of these findings through the peer review process ensures their reliability and establishes them as a basis for future investigations. This work exemplifies how cutting-edge research can bridge the gap between basic science and translational applications, potentially impacting individuals with mood disorders in the coming years.