New drug prevents weight gain even when following a diet rich in sugar and fat!

Researchers have developed a small molecule drug that prevents weight gain and harmful liver changes in mice fed a high-sugar, high-fat Western diet for life.

“When we give the mice this drug for a short time, they start to lose weight, and they all get thin,” said Dr. Madesh Muniswamy, MD, professor of medicine at the Joe R. and Teresa Lozano Long School of Medicine at the University of Texas School of Medicine at San Antonio.
The findings, by researchers from the University of Texas as well as the University of Pennsylvania and Cornell University, are published in the journal Cell Reports.

The research team discovered the drug by exploring how magnesium affects metabolism, which is the production and consumption of energy in cells. This energy, called ATP, fuels the body’s processes.

Magnesium plays many key roles in good health, including regulating blood sugar and blood pressure and building bone. But researchers have found that too much magnesium slows energy production in the mitochondria, which are the power stations for cells, where they take in nutrients and make energy that the rest of the cell can use.

“He’s hitting the brakes, he’s slowing down,” said co-lead author Travis R. Madaris, a doctoral student in Muniswamy’s lab at the University of Texas School of Medicine at San Antonio.

Deletion of MRS2, a gene that promotes the transport of magnesium into the mitochondria, led to more efficient metabolism of sugar and fat in power plants. The result: slim, healthy mice.
The rodents’ liver and fat tissue showed no evidence of fatty liver disease, a complication related to poor diet, obesity and type 2 diabetes.

The drug, which the researchers called CPACC, achieves similar results, restricting the amount of magnesium transported to the power plants.

And in the experiments, the result was again: skinny, healthy mice. With that, the University of Texas School of Medicine at San Antonio filed a patent application on the drug.

The mice served as a model system for long-term nutritional stress precipitated by a Western diet high in calories, sugar and fat. Common results of this stress are obesity, type 2 diabetes and cardiovascular complications.

“Reducing mitochondrial magnesium attenuated the harmful effects of prolonged nutritional stress,” said co-lead author Manigandan Venkatesan, a postdoctoral fellow in Muniswamy’s lab.

Muniswamy explained, “These results are the result of several years of work. A drug that can reduce the risk of cardiovascular diseases such as heart attack and stroke, as well as reduce the incidence of liver cancer that can follow fatty liver disease, will have a significant impact.” We will continue to develop it.”