Novel Drug Makes Mice Skinny Even on Sugary, Fatty Diet

When we give this drug to the mice for a short time, they start losing weight. They all become slim,” said Madesh Muniswamy, PhD, professor of medicine in the health science center’s Joe R. and Teresa Lozano Long School of Medicine.

Magnesium is the fourth most abundant element in the body, and plays many key roles in good health. But the researchers found that too much magnesium slows energy production in mitochondria.

Deleting MRS2, a gene that promotes magnesium transport into the mitochondria, resulted in more efficient metabolism of sugar and fat in the power plants. The result: skinny, healthy mice.

The drug, which the researchers call CPACC, accomplishes the same thing. It restricts the amount of magnesium transfer into the mitochondria.

The research team discovered the drug by first exploring how magnesium impacts metabolism, which is the production and consumption of energy in cells. 

The mice served as a model system of long-term dietary stress precipitated by the calorie-rich, sugary and fatty Western diet. The familiar results of this stress are obesity, type 2 diabetes and cardiovascular complications.

Liver and adipose (fat) tissues in the rodents showed no evidence of fatty liver disease, a complication related to poor diet, obesity and type 2 diabetes.

“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. We will continue its development.” Muniswamy said.

Sources:

Travis R. Madaris, Manigandan Venkatesan, Soumya Maity, Miriam C. Stein, Neelanjan Vishnu, Mridula K. Venkateswaran, James G. Davis, Karthik Ramachandran, Sukanthathulse Uthayabalan, Cristel Allen, Ayodeji Osidele, Kristen Stanley, Nicholas P. Bigham, Terry M. Bakewell, Melanie Narkunan, Amy Le, Varsha Karanam, Kang Li, Aum Mhapankar, Luke Norton, Jean Ross, M. Imran Aslam, W. Brian Reeves, Brij B. Singh, Jeffrey Caplan, Justin J. Wilson, Peter B. Stathopulos, Joseph A. Baur, Muniswamy Madesh. Limiting Mrs2-dependent mitochondrial Mg2+ uptake induces metabolic programming in prolonged dietary stress. Cell Reports, 2023; 42 (3): 112155 DOI: 10.1016/j.celrep.2023.112155

University of Texas Health Science Center at San Antonio. “Novel drug makes mice skinny even on sugary, fatty diet: Compound limits magnesium transport in cellular power plants called mitochondria..” ScienceDaily. ScienceDaily, 22 March 2023. <www.sciencedaily.com/releases/2023/03/230322082730.htm>.

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