A groundbreaking study published in eLife has established a significant connection between zinc levels and the risk of developing type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The research highlights the essential role zinc plays in metabolic processes, offering potential new approaches for managing these widespread health conditions.
Scientists have long understood the importance of zinc in the body, especially in insulin production and glucose metabolism. This new study, however, adds a new layer of understanding by revealing how variations in genes related to zinc regulation could influence disease susceptibility. By using advanced genetic techniques, the research team explored how these gene variations impact metabolic pathways, leading to deeper insights into how zinc affects metabolic health.
A key discovery in the study was the identification of rare mutations in the SLC39A5 gene, which controls zinc transport. These mutations were linked to higher zinc levels in the blood and a lower risk of developing type 2 diabetes. This suggests that zinc regulation could potentially act as a protective mechanism against metabolic disorders, opening doors to new preventive strategies.
Dr. Shek Man Chim, the lead author of the study and Principal Scientist at Regeneron Pharmaceuticals, emphasized that increasing zinc intake has already shown positive effects in improving blood glucose control among people with prediabetes and type 2 diabetes. “People with mutations in the key zinc transporter protein have a reduced risk of diabetes,” Chim explained.
The researchers further investigated this genetic link by analyzing data from the Regeneron Genetics Center-Geisinger Health System DiscovEHR study, which included participants of European ancestry. Their findings were confirmed through a meta-analysis of over 580,000 individuals, which established that elevated zinc levels—attributable to SLC39A5 mutations—were associated with a reduced risk of type 2 diabetes.
To strengthen their conclusions, the team conducted experiments on genetically modified mice that lacked the SLC39A5 transporter protein. These mice, despite being fed a high-fat diet, exhibited significantly lower fasting glucose levels and improved insulin sensitivity, both of which are crucial factors in the prevention of diabetes.
In addition to the potential benefits for diabetes, the study also examined the link between zinc and non-alcoholic fatty liver disease. Given the frequent overlap between diabetes and NAFLD, the researchers investigated whether the absence of the SLC39A5 transporter could protect the liver. The results were promising: mice without the SLC39A5 gene showed less fat accumulation in the liver and better insulin sensitivity, even when subjected to liver-damaging diets.
Moreover, these mice displayed lower markers of liver inflammation and fibrosis, which are associated with the progression of NAFLD to non-alcoholic steatohepatitis (NASH)—a more severe form of liver damage. However, the research team acknowledged that the results showed gender-specific differences in metabolic responses, suggesting that further studies are needed to fully understand these effects.
Dr. Harikiran Nistala, senior author and Head of Functional Genomics at Alkermes Inc., summarized the significance of these findings: “This study provides the first genetic evidence of zinc’s protective role against high blood sugar, shedding light on the underlying biological mechanisms. Our work suggests that targeting the SLC39A5 gene could open new avenues for treating type 2 diabetes and other related conditions where zinc supplementation alone is not enough.”
The study’s findings may represent a crucial step forward in combating the global rise of type 2 diabetes and metabolic diseases, offering hope for new treatment strategies and preventive measures.
In light of these discoveries, it may also be beneficial to examine dietary sources of zinc. Foods such as oysters, red meat, poultry, seafood, nuts, seeds, beans, and whole grains are rich in zinc. However, it is important to consider factors that may affect zinc absorption, such as phytates found in legumes and whole grains. Consulting a healthcare provider is recommended for those concerned about their zinc intake, particularly for individuals at risk of diabetes.
As the fight against metabolic diseases intensifies, this research may serve as a crucial turning point in developing more effective therapies and prevention methods.
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