Scientists Discover a Protein Switch That Burns Fat and Blocks New Fat Cells

A Protein That Determines the Fate of Fat

Modern weight-loss medications have transformed obesity treatment, but they often come with a drawback: they can reduce muscle mass. Now, scientists at the Weizmann Institute of Science have uncovered a biological mechanism that may one day address that challenge while boosting the body’s ability to burn fat. The team identified a protein called MTCH2, nicknamed ‘Mitch’, that appears to play a major role in how cells manage energy and store fat. In a recent study published in the EMBO Journal, the researchers found that disabling this protein in human cells increases the rate at which fats and carbohydrates are burned while also reducing the formation of new fat cells.

A Surprising Discovery in Mice

Several years ago, Prof. Atan Gross and his colleagues made an unexpected observation while studying Mitch in mice. When they suppressed the protein in mouse muscle tissue, the animals showed major improvements in body composition: they not only avoided obesity but also developed more muscle fibers. These fibers consume large amounts of oxygen and are associated with improved stamina and athletic performance. The mice performed better in physical stress tests and showed improved heart function. This raised a key question: How could disabling a single protein both protect against obesity and enhance endurance?

The Role of Mitochondria

To answer that, researchers turned to mitochondria, the power plants of cells. Their shape and organization reveal how cells produce energy. Sometimes mitochondria fuse into large interconnected networks that generate energy efficiently; other times they remain separate and less efficient. When energy production becomes less efficient, cells compensate by consuming more fuel, including fats, carbohydrates, and proteins. Gross’s team discovered that Mitch helps control this process by regulating mitochondrial fusion.

Experiments on Human Cells

The new study, led by doctoral student Sabita Chourasia, used genetic engineering to eliminate Mitch from human cells. The results were dramatic: without Mitch, the normal mitochondrial network broke apart into separate units, making energy production less efficient and leaving cells in a constant state of energy shortage. While this might seem harmful, such inefficiency can actually favor increased energy expenditure and reduced fat storage. “After deleting Mitch, we examined, every few hours, the effect on more than 100 substances involved in metabolism in human cells,” Chourasia explains. “We saw an increase in cellular respiration—the process by which the cell produces energy from nutrients using oxygen. This explains the increased muscular endurance in previous mouse experiments.”

Fat Becomes the Primary Fuel

Because the altered cells needed more energy, they consumed more available fuel. Researchers observed greater breakdown of fats, carbohydrates, and amino acids. Notably, there was a shift in energy production: ordinary cells rely more on carbohydrates and proteins, but cells lacking Mitch depended much more on fat as their primary fuel source. “We discovered that deleting Mitch led to a major drop in fats in membranes,” Gross says. “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.”

Blocking New Fat Cell Formation

The researchers also found that removing Mitch affects the creation of new fat cells. Previous studies showed that women with obesity tend to have elevated levels of Mitch. That led the team to investigate whether Mitch influences the formation of new fat cells, which originate from progenitor cells. Under normal conditions, these immature cells accumulate fat and develop into mature fat-storing cells through differentiation. When Mitch was removed from progenitor cells, this transformation became much more difficult. “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 explains. “Reducing the ability to synthesize membranes prevents the cells from growing, developing, and reaching the point where differentiation is possible. The process of fat accumulation requires a large amount of available energy, but in cells without Mitch, there is a shortage of energy. In addition, the expression of genes necessary for differentiation is suppressed. As a result, differentiation of new fat cells is reduced, along with fat accumulation.”

Potential for New Obesity Treatments

Although the work was conducted in cells and is still far from becoming a treatment, the findings reveal a powerful biological pathway that influences both energy use and fat storage. By increasing fat burning while limiting new fat cell formation, targeting Mitch could eventually provide researchers with a new strategy for combating obesity. The discovery may also help address one of the most persistent challenges of modern weight-loss therapies: preserving healthy muscle while reducing excess body fat. The study involved researchers from the Weizmann Institute of Science, the University of Pennsylvania, and the University of Texas at San Antonio.