Could a single protein hold the key to a new generation of obesity treatments? Mitch, please!
That’s what scientists are saying and hoping after discovering the surprising role of MTCH2 — a protein they’ve nicknamed Mitch — that appears to have a major influence on how cells manage energy and store fat.
In a new study, researchers discovered that disabling this protein supercharged the cells’ ability to burn carbohydrates and fat while also blocking the formation of new fat cells.
This findings are especially exciting because they point to a potential new approach to obesity treatment that could also overcome the loss of muscle mass, one of the biggest drawbacks of today’s blockbuster weight loss drugs.
The breakthrough has been years in the making.
Researchers at the Weizmann Institute of Science first encountered Mitch’s surprising powers while studying mice.
When they suppressed production of the protein in the animals’ muscle tissue, they noticed something unexpected. The mice didn’t just stay lean. They became remarkably resistant to obesity, developed more muscle fibers associated with improved stamina and athletic performance and performed better during physical stress tests.
Researchers also observed improvements in heart function, suggesting the protein’s influence extended well beyond body fat.
These striking results motivated scientists to find out whether the same thing happened in human cells.
Researchers found that removing Mitch effectively tricked cells into acting as though they were experiencing a constant energy shortage. To compensate, the cells ramped up their fuel compensation, burning significantly more fats, carbohydrates and amino acids to keep up with their energy demands.
In other words, disabling a single protein appeared to flip cells into a higher-energy, higher-fat-burning mode.
Normally, cells tend to rely more heavily on carbohydrates and proteins as readily available fuel sources. But cells without Mitch shifted much more aggressively toward burning fat, suggesting the protein serves a metabolic traffic controller that helps determine whether fat gets stored away or used for energy.
“We discovered that deleting Mitch led to a major drop in fats in membranes,” co-author Atan Gross explained to ScienceDaily.
“At the same time, we saw an increase in fatty substances used to produce energy, and we realized that the fat was being broken down from the membrane to be used as fuel.” In other words, we showed that Mitch determines the fate of fat in human cells.”
The researchers uncovered another surprising benefit.
When they removed Mitch from progenitor cells — immature cells that can eventually develop into mature fat-storing cells — the process of creating new fact cells became much more difficult.
Instead of readily accumulating fat, the cells appeared stuck in an environment that wasn’t favorable for producing it in the first place.
“When we deleted Mitch from the progenitor cells, we discovered that the environment created in these cells was not conducive to the synthesis of new fats,” Gross explained.
The discovery suggests that Mitch doesn’t just influence how existing fat is burned, but may also play a key role in determining whether new fact cells are created at all.
The findings are especially intriguing because preserving muscle has become one of the biggest challenges in modern weight loss medicine. Researchers have been searching for ways to maximize fat loss while protecting muscle, and Mitch may offer an important clue.
That doesn’t mean that a Mitch-targeting drug is around the corner.
Much more work is needed before scientists know whether targeting the protein can be done safely or effectively in people.
Still, the findings identify a promising new biological pathway that could eventually inspire therapies capable of increasing fat burning, preventing the formation of new fat cells and preserving healthy new muscle.
“We showed that Mitch determines the fate of fat in human cells,” said Gross.
