A groundbreaking study published in the Journal of Physiology has revealed a remarkable connection between the liver and the brain, suggesting that ketones produced by the liver—especially during exercise—play a key role in keeping the brain healthy and maintaining memory function. The latest research, conducted by a team from the University of Missouri, shows that when the liver’s ability to produce ketones is blocked, rats experience memory deficits and diminished brain mitochondrial function, but that regular endurance training can effectively reverse these cognitive problems, even when ketone production is hampered (psypost.org).
The significance of this discovery resonates particularly in Thailand, where the prevalence of liver-related conditions such as Steatotic Liver Disease—a growing problem due to dietary shifts and aging—may inadvertently affect public cognitive health. Regular exercise habits and care for liver health could thus offer a double-edged sword for defending both physical and mental wellbeing among Thais as they age.
For decades, medical researchers have endorsed the brain-boosting benefits of physical activity, which include stimulating new brain cell growth, fortifying synaptic connections, and invigorating mitochondrial health—the “energy factories” of brain cells. Recent theories had posited ketone bodies — molecules the liver generates during fasting or exertion — as a possible link in this chain, because they serve as an alternative energy source for the brain. Among them, beta-hydroxybutyrate has attracted attention for its ability to dampen oxidative stress, heighten mitochondrial efficiency, and foster adaptive brain changes central to learning and memory (Journal of Physiology).
But how vital are these liver-derived ketones to brain health? And does exercise exert its neuroprotective effects via this pathway? To answer these questions, the research team used gene-editing tools to silence a crucial liver enzyme—3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2)—key to ketone production in healthy rats. This allowed them to observe what happened when rats exercised but their livers could not make enough ketones.
The results were compelling. When the ability to produce liver ketones was diminished, rats not only displayed impaired spatial memory (as measured by time spent exploring the novel segment of a Y-maze) but also showed clear signs of mitochondrial dysfunction in the frontal cortex of the brain. Detailed protein analyses corroborated these findings, showing reduced activity in brain pathways crucial for energy production and learning. This mitochondrial dysfunction emerged even though the rats had no other symptoms of neurodegeneration, suggesting that liver-derived ketones themselves are crucial for everyday brain function, not just as a reserve fuel in crisis.
“Exercise can still protect the brain, even when the liver’s ability to make ketones is suppressed, which may be relevant to those with liver disease,” noted the study’s lead authors, a professor and a postdoctoral researcher from the University of Missouri, in an interview with PsyPost. They emphasized how exercise training over several weeks reversed the negative effects of ketone suppression. Rats that engaged in regular endurance running regained healthy mitochondrial function and performed just as well as control animals in cognitive tests, despite their impairment in ketone production. Proteomic studies suggested this recovery was tied to improved synaptic plasticity — how efficiently neurons can adapt to new tasks.
The Thai context gives these results added urgency. With liver-related diseases on the rise—especially in regions with high rates of fatty liver or metabolic syndrome—an increasing segment of the population may be at unknowingly greater risk for cognitive decline. The new research suggests that regular exercise might serve as a powerful “backup” brain defense, providing neuroprotective effects even if liver ketone levels are diminished due to underlying disease. For older Thais worried about conditions like Alzheimer’s, or those who already experience compromised liver function, adopting regular exercise regimens could substantially improve future quality of life—a message that aligns with long-standing wisdom in Thai wellness culture, where movement and balanced diets feature prominently (World Health Organization Thailand).
This study also highlights a rich area for medical advancement and policy intervention. As the lead authors explain, future research could target ways to enhance ketone production in the liver or improve how the brain uses ketones, with the goal of preventing or even treating neurodegenerative disorders. Such strategies would be of particular interest in Thailand, where the rapidly ageing demographic is projected to sharply increase the incidence of age-related cognitive impairment in the coming decades (UNFPA Thailand).
The research also underscores long-standing limitations. The study was performed exclusively on female rats, leaving open questions about generalizability to males or to humans. The cognitive tests, using the Y-maze, may have limitations in capturing subtle improvements in cognition, and HMGCS2 silencing only partially reduced—rather than eliminated—ketone production, pointing to compensatory mechanisms that remain to be explored. There is also a need to clarify which alternative pathways exercise engages to benefit the brain when normal ketone metabolism is not possible.
Nonetheless, practical lessons for Thai readers are clear. According to data from Thailand’s Ministry of Public Health, non-alcoholic fatty liver disease (NAFLD) is now common in the Thai population, associated with rising levels of obesity, diabetes, and other metabolic disorders (Thai Health 2022). This convergence of risk factors does not simply threaten liver health, but may also undermine cognitive resilience among older adults, potentially increasing the country’s health burden and economic costs Bangkok Post.
Moreover, the findings resonate with Buddhist teachings and Thai cultural traditions that link the mind and body in holistic health. The idea that a healthy lifestyle—balancing activity, nutrition, and moderation—safeguards both brain and body has deep roots in local wisdom. The integration of cutting-edge science with these cultural values supports a modern “whole health” approach recommended by Thailand’s leading neurologists and lifestyle medicine practitioners.
Looking ahead, Thai policymakers, health professionals, and individuals can take this knowledge to heart by encouraging more exercise opportunities in community spaces, expanding screening for liver diseases in at-risk populations, and fostering greater public discourse on metabolic and cognitive health. Research funding agencies may wish to support studies on exercise-based interventions for preserving cognitive function, particularly in elderly Thais living with liver conditions or at risk of dementia. Families can help by participating in group activities, fitness campaigns, or community walking groups, using both tradition and innovation to create healthier futures.
The actionable recommendation for Thai readers is straightforward: maintain regular physical activity, especially endurance exercises like brisk walking, jogging, or cycling, which are increasingly accessible in urban and rural areas alike. Eating a well-balanced Thai diet rich in vegetables, whole grains, and healthy fats may also support optimal liver and brain function. Finally, regular check-ups for metabolic health (including tests for fatty liver) and engagement in cognitive activities are prudent steps that honor both modern science and cherished Thai values.
In summary, the new research reveals that the liver and brain are deeply intertwined partners in the dance of health, especially in the context of exercise. Even when one partner falters, the other can compensate, underscoring the resilience of the human body—and the enduring importance of holistic lifestyle choices for maintaining mental clarity and cognitive vitality throughout life.