Researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have unveiled an experimental drug that successfully curbed weight gain and protected liver health in mice subjected to a high-sugar, high-fat diet throughout their lives.
The newly developed small-molecule drug, known as CPACC, emerged from a comprehensive effort led by UT Health San Antonio to tackle mitochondrial abnormalities linked to conditions like obesity, diabetes, and cardiovascular disease. CPACC operates by regulating the entry of magnesium into mitochondria, the cell components responsible for energy production and calorie burning.
Madesh Muniswamy, molecular biochemist at UT Health San Antonio and senior author of the study, emphasized, “These findings are the result of several years of work.”
Magnesium’s Role in Health and Energy Regulation Magnesium is one of the major positively charged ions integral to various cellular functions within the body. While it plays a crucial role in health maintenance, such as blood sugar and blood pressure regulation, excessive magnesium can hamper energy production in mitochondria.
Travis Madaris, biologist at UT Health San Antonio and co-lead author of the study, illustrated, “It puts the brake on, it just slows down.”
Discovering CPACC’s Potential The researchers stumbled upon CPACC while exploring the effects of deleting the MRS2 gene, responsible for encoding a magnesium transporter protein called Mrs2. This protein functions as a channel for magnesium transport across mitochondrial membranes.
Their investigations delved into the impact of a prolonged high-fat, high-sugar, and high-calorie Western diet on regular mice compared to mice with a deleted MRS2 gene. The MRS2 deletion resulted in leaner, healthier mice exhibiting enhanced mitochondrial sugar and fat metabolism. Interestingly, these benefits persisted even after a year of consuming the Western diet from 14 weeks of age.
Promising Results and Insights The liver plays a pivotal role in regulating sugar and fat metabolism, especially in response to eating and fasting. Remarkably, the mice with MRS2 deletion showed no signs of fatty liver disease, a condition often triggered by imbalanced diets, obesity, or type 2 diabetes.
Further experiments involving CPACC administration replicated the effects observed with MRS2 gene deletion. The drug effectively impedes magnesium channeling encoded by the gene, leading to lean and healthy mice due to reduced magnesium transport into mitochondria.
Considerations and Future Prospects While these findings offer potential insights, it’s essential to note that results in mice might not directly translate to humans. The researchers acknowledge some limitations, including the extended use of dietary stress to mimic metabolic syndrome in humans. Further investigations could shed light on the primary impacts of MRS2 deletion under short-term dietary stress. Additionally, the researchers highlight the need to explore MRS2’s effects on various organs beyond metabolic regulation.
A Path Forward The research team has filed a patent application for CPACC, indicating the drug’s potential therapeutic implications. Madesh Muniswamy remarked, “A drug that can reduce the risk of cardiometabolic diseases such as heart attack and stroke, and also reduce the incidence of liver cancer, which can follow fatty liver disease, will make a huge impact.”
While human applications of CPACC await further research and validation, this experimental drug opens a promising avenue for addressing weight-related health challenges and promoting liver health.
By Impact Lab