Methylmercury can accumulate in water environments and enter the food chain. Human exposure is of particular concern in communities affected by contaminated rivers, industrial pollution, artisanal gold mining and environmental disasters. Mercury pollution is usually associated with damage to the brain and nervous system. However, this new study suggests that methylmercury may also disrupt the body's metabolic health, affecting the liver, fat tissue biology and cardiovascular disease risk in vulnerable populations.
The study is a collaboration of researchers with expertise in toxicology, tissue biology, metabolism, computational modelling and advanced image analysis, from the University of Bristol (UK), the Federal University of Ceará, Brazil, and the University of California, USA.
The team looked at a protein called apolipoprotein E (ApoE), which helps the body transport fats and cholesterol around the bloodstream. ApoE also plays a role in inflammation, liver health and heart disease risk. The study aimed to find out whether differences in this protein could make some people more vulnerable to the harmful effects of methylmercury.
The team wanted to find out whether a person's ApoE type affects how their body responds to mercury exposure. Using computer modelling, the researchers explored how methylmercury might interact with different human ApoE forms. Their results suggested that two forms, ApoE2 and ApoE3, may bind more strongly to methylmercury, while another form, ApoE4, did not show stable binding.
The team then sought to explore whether differences in ApoE biology influence how individuals respond to mercury exposure. To explore this further, researchers used animal models (mice) that do not produce ApoE and are commonly used to study problems with blood fats and heart disease risk.
When these models were exposed to methylmercury, they experienced more negative health effects than expected. These effects included higher levels of cholesterol and blood fats, signs of liver damage, increased stress on cells, and alterations in body fat. Overall, the findings suggest that when ApoE is not working properly, the body may be less able to cope with mercury exposure, making the body more vulnerable to the harmful effects of mercury.
The team then studied mice lacking ApoE. When methylmercury exposure was combined with ApoE deficiency, the animals showed stronger signs of metabolic disruption, including higher cholesterol and triglycerides, increased markers of liver injury, oxidative stress and changes in white fat tissue.
Dr Augusto Coppi, Senior Lecturer in Veterinary Anatomy at the University of Bristol and co-lead of the study, said: "Mercury pollution is usually viewed through the lens of neurotoxicity, but our findings suggest that its impact may reach much further. Our study indicates that methylmercury can interact with key biological systems involved in cholesterol handling, liver health and fat tissue function.
"In simple terms, the findings suggest a possible double hit: methylmercury exposure on one side and pre-existing vulnerability in lipid metabolism on the other. Together, these factors may place greater stress on organs and tissues involved in metabolic and cardiovascular health.
"Bristol's expertise in 3D quantitative image analysis is enabling the team to examine tissue architecture in far greater detail — moving beyond whether organs simply look abnormal to measuring how methylmercury exposure and ApoE-related vulnerability may alter metabolically important tissues. This ongoing work will support deeper tissue-level interpretation and help clarify the study's potential translational relevance for public health."
The authors emphasize that the study should not cause alarm about normal dietary choices, but it does highlight the need to understand how pollution, genetics, nutrition and metabolic health may interact.
The findings are especially relevant for future research into people already at higher risk of metabolic or cardiovascular disease, including those with high cholesterol, liver stress or ApoE-related vulnerability. They may also help guide future nutritional or public health strategies for populations exposed to high levels of mercury contamination.
Professor Reinaldo B. Oriá, corresponding and co-lead author from the Federal University of Ceará, said: "This work reflects the value of long-standing international collaboration. By combining expertise across countries and disciplines, we were able to ask not only whether methylmercury is toxic, but who may be more vulnerable and how future interventions might reduce that risk."
This was a preclinical study using a high-dose methylmercury exposure model. The findings should not be directly extrapolated to everyday low-level exposure in the general population. Further studies, including research in human populations, are needed.
Paper
'In silico ApoE isoform interactions with methylmercury (MeHg) and in vivo MeHg intoxication effects on epididymal white fat tissue and liver function in young ApoE knockout mice' by Augusto Coppi, Reinaldo B. Oria et al. in Chemical Research in Toxicology.
