One Molecule Could Help Researchers Treat Obesity

By Rita Waimer

A recently identified molecule could unlock a new method of losing weight. Writing in the May 14, 2020 issue of Nature Communications, Virginia Tech scientists describe BAM15, a mitochondrial uncoupler that helps mice burn fat without eating less, losing muscle mass, or raising body temperature.

How It Works

BAM15 essentially kicks cell metabolism into overdrive. As you may know, the mitochondria is the powerhouse of the cell, burning nutrients in order to make the ATP that helps our bodies function properly. The cell creates ATP when protons pass through an enzyme embedded in the cell membrane called ATP synthase.

Mitochondrial uncouplers like BAM15 transport protons and bypass ATP synthase. This interrupts the process of creating ATP and makes cells work harder. The result is that cells burn more calories — all without us doing any exercise.

Changing a cell’s metabolism can, of course, produce effects beyond what the scientists were looking for, so they were careful to ensure that their drug was reaching the intended targets and safe to use. After a series of studies in mice, they found that BAM15 isn’t toxic, even at high doses. And unlike some weight-loss drugs, it doesn’t affect the satiety center of the brain, which tells the body if it’s hungry or full. The researchers also concluded that body temperature was unaffected by BAM15.

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However, the scientists observed a relatively short half-life for BAM15 in their mouse models, which means it wasn’t effective for very long. To be viable as a pill for humans, the half-life would need to be much longer. So while BAM15 might not be used to treat humans, a similar molecule could.

The team is now looking for a suitable replacement. “So far, we have made several hundred molecules related to this,” said Webster Santos, the Cliff and Agnes Lilly Faculty Fellow of Drug Discovery in the College of Science at Virginia Tech and one of the study’s authors.

Possible Uses

With more than 40 percent of American adults affected by obesity, a drug that can help patients lose weight and keep it off could be widely beneficial. Plus, the drug could help treat and prevent several other diseases linked to obesity: cardiovascular disease, diabetes, and, critically, nonalcoholic steatohepatitis (NASH).

NASH is a type of fatty liver disease that causes inflammation and fat accumulation in the liver, and it’s expected to become a leading cause of liver transplants in the United States. Creating a new treatment for NASH is one of the main goals for Santos and his team, and they’re now working to transition their treatment from animals to humans. So far, their compounds have proven to effectively treat NASH in mice.

The team is also examining the anti-oxygen effect of mitochondrial uncouplers. The effect can minimize oxidative stress in our bodies, and therefore could help slow neurodegeneration and aging. If so, they could use mitochondrial uncouplers to minimize the risk of Alzheimer’s disease and Parkinson’s disease.

If these new treatments prove to be safe and effective, they could help people all over the world live healthier, longer lives.


Discussion Questions

  • What other diseases could this new drug help treat?
  • What is the natural function of mitochondrial uncouplers?

Vocabulary

  • ATP
  • Half-life
  • Mitochondrial uncoupler
  • Neurodegeneration