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

“When we give this drug to the mice for a short time, they start losing weight. They all become slim,” said the senior author.

Findings were published in the high-impact journal Cell Reports.

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

Magnesium is the fourth most abundant element in the body after calcium, potassium and sodium, and plays many key roles in good health, including regulating blood sugar and blood pressure and building bones. But the researchers found that too much magnesium slows energy production in mitochondria, which are cells’ power plants.

“It puts the brake on, it just slows down,” said a co-lead author.

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.

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.

The drug, which the researchers call CPACC, accomplishes the same thing. It restricts the amount of magnesium transfer into the power plants. In experiments, the result was again: skinny, healthy mice.

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.

“Lowering the mitochondrial magnesium mitigated the adverse effects of prolonged dietary stress,” said another co-lead author.

https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00166-3

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