A new study in the Journal of Physiology reveals a strong connection between the liver and the brain. Liver-produced ketones, especially during exercise, appear to support brain health and memory. In rats, hindering the liver’s ketone production led to memory deficits and reduced brain mitochondrial function, while sustained endurance training reversed these effects even when ketone production was impaired. These findings come from researchers at a major U.S. university and were summarized by PsyPost.
This research resonates in Thailand, where rising rates of fatty liver disease and metabolic disorders threaten both physical and cognitive wellbeing. Promoting liver health and regular exercise could thus offer dual benefits for aging Thais, aligning with local emphasis on balanced living and preventive care.
For years, science has highlighted exercise as a booster for brain health—stimulating neuron growth, strengthening synapses, and supporting mitochondrial energy production. Ketone bodies, produced by the liver during fasting or exertion, have been proposed as a key energy source for the brain. Among these, beta-hydroxybutyrate has attracted attention for reducing oxidative stress, boosting mitochondrial efficiency, and supporting adaptive brain changes linked to learning and memory.
To test the ketone-brain connection, researchers used gene-editing to suppress a critical liver enzyme, HMGCS2, essential for ketone production. This allowed them to observe brain function when rats exercised but could not produce normal levels of ketones.
Results showed clear effects. With reduced liver ketone production, rats had impaired spatial memory in a Y-maze test and signs of mitochondrial dysfunction in the frontal cortex. Protein analyses confirmed weaker activity in brain energy and learning pathways. The findings suggest liver-derived ketones support everyday brain function, not merely crisis responses.
Lead authors noted that exercise could still protect the brain even if ketone production is compromised, a finding particularly relevant for individuals with liver disease. Weeks of endurance training reversed the negative effects, restoring mitochondrial function and cognitive performance. Proteomic data indicated improved synaptic plasticity accompanying this recovery.
Thai readers can draw practical implications from these results. NAFLD and other metabolic conditions are increasingly prevalent in Thailand, potentially increasing risk for cognitive decline with age. The study implies that regular exercise may serve as a robust defense for brain health, even when liver function is challenged. This aligns with Thai wellness traditions that emphasize movement, balance, and preventive care, and resonates with health guidance from national and regional health authorities.
Policy and research implications are also clear. Future work may focus on boosting liver ketone production or enhancing brain ketone utilization to prevent or treat cognitive decline. In Thailand, an aging population makes such research and targeted interventions particularly valuable, supporting broader efforts to reduce the burden of dementia and metabolic disease.
The study has limitations. It used female rats, so questions remain about applicability to males and humans. Y-maze testing captures certain aspects of memory but may miss subtler changes. Also, silencing HMGCS2 reduced, rather than eliminated, ketone production, suggesting other pathways may contribute to brain resilience and warrant further study.
For Thai readers, the takeaway is actionable. Thailand’s health data show rising NAFLD prevalence alongside obesity and diabetes, which could impact cognitive resilience as people age. Encouraging physical activity across communities—through walking groups, cycling paths, and accessible fitness programs—can support both liver and brain health. A balanced Thai diet rich in vegetables, whole grains, and healthy fats complements these efforts, alongside regular metabolic health check-ups and cognitive activities.
In sum, the study reinforces the liver-brain partnership and the protective power of exercise. Even when one metabolic pathway falters, the other can sustain brain function, highlighting the value of holistic lifestyle choices for maintaining mental clarity and cognitive vitality throughout life in Thailand.