Experimental Drug Protects Mice from Weight Gain and Liver Damage Due to High-Sugar Diet
Researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have developed an experimental drug that has shown promising results in protecting mice from weight gain and liver damage caused by a high-sugar, high-fat diet. The drug, known as CPACC, works by limiting the entry of magnesium into the mitochondria, which are responsible for generating energy and burning calories in cells.
The study, led by UT Health San Antonio molecular biochemist Madesh Muniswamy, aimed to investigate the effects of deleting a specific gene called MRS2, which encodes a magnesium transporter protein known as Mrs2. This protein acts as a channel to transport magnesium across the mitochondrial membrane. The researchers compared the effects of a long-term high-fat, high-sugar Western diet on normal mice and mice with the MRS2 gene deleted.
The findings revealed that mice with the MRS2 gene deleted remained leaner and healthier compared to normal mice, despite consuming the Western diet for up to a year. These mice also showed improved sugar and fat metabolism in their mitochondria. Importantly, there were no signs of fatty liver disease, which can result from an unbalanced diet, obesity, or type 2 diabetes.
The team then tested the effects of the experimental drug CPACC on the mice and found that it produced the same results as the deletion of the MRS2 gene. The drug works by inhibiting the magnesium channels that the gene encodes for, reducing the amount of magnesium transported into the mitochondria and resulting in leaner, healthier mice.
It is important to note that although the results are promising, they have only been observed in mice, and further research is needed to determine if the same effects can be replicated in humans. The study also acknowledges some limitations, such as the use of long-term dietary stress to mimic metabolic syndrome in humans. Additionally, the complete deletion method used for the MRS2 gene makes it difficult to study its effects on individual tissues and organs.
Despite these limitations, the researchers have filed a patent application for CPACC, highlighting its potential to reduce the risk of cardiometabolic diseases such as heart attack, stroke, and liver cancer, which can be associated with fatty liver disease. The team plans to continue developing the drug and further investigate its effects on various organs.
The study, published in Cell Reports, marks a significant step forward in understanding the role of mitochondrial abnormalities in obesity, diabetes, and cardiovascular disease. Continued research in this area could potentially lead to new treatments and preventive measures for these conditions.