A groundbreaking new study published in the Journal of Physiology has unveiled a striking connection between the liver’s metabolic function and brain health, highlighting the crucial role of liver-produced ketones during exercise—and raising intriguing possibilities for combating cognitive decline, even among those with liver impairments. Conducted by researchers at the University of Missouri, the research demonstrates that when liver cells lose the ability to make ketones, cognitive and mitochondrial function in the brain suffer. Remarkably, endurance exercise was found to reverse these negative effects, suggesting a possible “backup system” that could protect the aging brain and offer new hope to individuals with liver disease (psypost.org).
For many Thais, the implications of this research extend beyond academic curiosity. As Thailand’s population ages rapidly and rates of non-alcoholic fatty liver disease (officially termed steatotic liver disease) continue to rise, understanding how the liver interacts with the brain is of growing public health importance. Memory decline, dementia, and Alzheimer’s disease are increasingly common, placing a heavy emotional and economic burden on families and the healthcare system. This research suggests that liver health may be much more important to brain function than previously understood—and, encouragingly, that regular physical activity can help protect the brain even in the face of hepatic challenges.
At the core of the study are ketone bodies—molecules the liver produces during periods of fasting and especially during sustained exercise. The most notable of these ketones, beta-hydroxybutyrate, can serve as an energy source for the brain and has been linked to enhanced mitochondrial function, reduced oxidative stress, and improved synaptic plasticity, all markers of cognitive health (NCBI). Scientists have long observed that regular exercise leads to better brain function and lowers the risk of dementia, but they had not shown unequivocally whether the cognitive benefits of exercise could be traced directly to ketone production in the liver.
To answer this, the University of Missouri team deployed a sophisticated viral technique in healthy, six-month-old female rats that selectively reduced the expression of the enzyme HMGCS2—a crucial driver of ketone production—in the liver. By knocking down this enzyme, they could observe what happens to cognitive function and brain cell metabolism when ketone output during exercise is severely restricted.
The animals were separated into several experimental groups: some remained sedentary, while others undertook either a single session or a four-week regimen of treadmill running. Blood ketone levels, mitochondrial function in the brain’s frontal cortex, and spatial memory performance using a Y-maze were measured. Additional tests on rat neuron-like cells assessed how genetic disruptions in ketone use affected cellular respiration.
The findings were striking: exercise normally boosted blood ketone levels and improved brain mitochondrial health, but in rats with impaired liver ketone production, these benefits were lost. The brains of these rats showed increased markers of mitochondrial dysfunction, decreased energy production, and less expression of proteins linked to learning and memory. Cognitively, they performed worse in spatial memory tasks—demonstrating, for the first time, that the liver’s ability to generate ketones during exercise is vital for optimum brain health.
Yet perhaps even more surprising was what happened in rats who, despite reduced liver ketone capacity, engaged in prolonged endurance training. Physical training restored cognitive performance and mitochondrial measures to normal, and molecular analysis revealed elevated markers for synaptic plasticity. This suggests that exercise may activate alternative pathways that compensate for the liver’s shortfall in ketone production. According to the authors, including the principal investigators and postdoctoral team members, “We also found that 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 that causes reduced ketone production.”
The research was supplemented by cell culture studies, showing that neurons must not only receive ketones but also retain the ability to metabolize them in order to maintain healthy mitochondrial respiration. In the context of Thailand, this dual importance of ketone production and utilization is especially relevant as metabolic disorders and liver diseases become more prevalent. Official statistics indicate that over 25% of the urban adult population in Thailand is affected by non-alcoholic fatty liver disease, which is often linked to diabetes and obesity—conditions that are also risk factors for cognitive decline (World Health Organization, Thailand profile).
Memory and learning are cultural touchstones in Thailand, underpinning everything from children’s education to the veneration of elders’ wisdom. The study’s assertion that “the body’s natural production of ketones is important for keeping the brain healthy” offers both a warning and an opportunity. On the one hand, it suggests that widespread liver conditions could inadvertently contribute to national rates of memory impairment and dementia. On the other, it highlights a path for intervention based not on expensive drugs but on exercise—a practice accessible to almost anyone and deeply rooted in aspects of Thai culture from morning group aerobics in public parks to the spiritual discipline of walking meditation.
Expert commentary from the researchers emphasizes practical takeaways: “Our findings suggest that taking care of the liver and understanding ketone metabolism could be a new way to help prevent or slow down brain diseases. This study highlights how important exercise is for brain health—especially for people who might have lower ketone production due to liver conditions like Steatotic Liver Disease.”
The lead researchers also underscored several limitations: their study focused exclusively on female rats, leaving questions about males and interspecies differences. The cognitive tasks tested only specific aspects of memory, and the genetic knockdown did not fully eliminate liver ketone production, suggesting that backup sources or mechanisms may exist.
For Thai clinicians, policymakers, and the general public, the takeaways offer cause for optimism but also underscore the urgency of preventative public health strategies. Medical experts from Thailand’s leading teaching hospitals often note a cultural reluctance to prioritize liver health compared to more immediately “visible” problems like diabetes or hypertension. But with brain health at stake, there may be new motivation to support liver-friendly diets—rich in vegetables, low in excessive simple sugars and alcohol—and to integrate regular endurance exercise into community routines.
Thailand’s revered tradition of Muay Thai and rising trends in running, cycling, and group fitness bode well for widespread engagement with the protective behaviors highlighted by this study. At the same time, the research speaks to families caring for elderly members: regular movement, even simple walking or low-impact group dance, could be a potent safeguard for cognitive performance.
Moving forward, researchers plan to investigate how this liver–brain connection plays out in actual disease contexts such as Alzheimer’s, and whether drugs or supplements that boost liver ketone production might serve as a new front in the fight against neurodegenerative disease. Moreover, there is interest in understanding the molecular pathways through which exercise “steps in” to protect the brain when the liver falls short—findings that could have wide-ranging public health and therapeutic implications not only in the West but across Asia, including Thailand.
For now, the message is clear: protecting liver health and prioritizing regular endurance exercise are not just good for the waistline or the heart—they may be vital tools for safeguarding the Thai mind and memory well into old age. All Thais, whether urban office workers, rural farmers, students, or elders, can benefit from reevaluating their daily physical activity and liver health management as an investment in lifelong cognitive vitality.
The key recommendation for readers is to make regular endurance exercise—such as brisk walking, cycling, group running, or even extended temple grounds walking—a priority, alongside seeking regular liver health screenings. Those with diagnosed liver conditions should consult with healthcare professionals about safe ways to incorporate fitness into their routines. As knowledge of the liver–brain connection grows, Thai society holds the potential to transform emerging science into practical, culturally resonant public health action.
Sources: PsyPost, Journal of Physiology, World Health Organization, NCBI