Scientists have discovered a protein switch that determines whether cells burn fat or store it. Turning off this protein boosts fat burning and hinders the creation of new fat cells, suggesting a new way to treat obesity. Later studies have supported this finding, showing that the same protein also helps control how much energy the body uses.
What if the key to combating obesity isn’t about reducing appetite, but about changing how cells use energy?
Researchers at the Weizmann Institute of Science have identified a protein called MTCH2, nicknamed "Mitch," which is crucial for metabolism. When scientists disabled this protein in lab experiments, cells started using more fuel, including fats and carbohydrates. They also found that removing Mitch interfered with the process by which immature cells become fat cells.
This discovery builds on earlier mouse experiments, where turning off Mitch in muscle tissue increased energy expenditure, improved endurance, and protected the animals from diet-induced obesity.
The findings, published in The EMBO Journal in January 2025, suggest that manipulating this protein could eventually offer a way to influence both fat burning and fat accumulation. Additional research published later that year has provided further evidence of its importance in regulating body fat and metabolism.
Over the past decade, medications designed to promote weight loss have transformed obesity treatment. Drugs such as semaglutide and tirzepatide have helped many patients achieve substantial reductions in body weight, largely by influencing appetite and the body's responses to food.
But losing weight does not necessarily mean losing only fat.
Weight reduction can also involve a decline in lean body mass, which includes muscle and other tissues. Preserving muscle is especially important because it supports strength, mobility, and metabolic health.
A 2026 analysis of 20 clinical trials involving 15,782 participants found that lean mass accounted for approximately 25% to 39% of the weight lost with several widely used weight-loss medications. Importantly, the researchers found that comparable proportional losses also occurred with lifestyle interventions, while adding resistance training helped preserve more lean tissue.
These concerns have encouraged scientists to investigate ways to reduce body fat while protecting the muscles needed for long-term health.
Professor Atan Gross and his colleagues at the Weizmann Institute arrived at a possible avenue through an unexpected discovery involving Mitch.
In earlier experiments, Gross's team reduced the activity of MTCH2 in the muscles of mice. The effects were striking.
The genetically modified animals showed increased metabolic activity and were resistant to obesity caused by their diet. Their muscles also developed more fibers with a high capacity for using oxygen, helping improve physical endurance.
The mice performed better in exercise and stress tests and showed improvements in heart function. In addition to resisting excess fat accumulation, they experienced favorable changes in their overall body composition.
The results suggested that Mitch was doing much more than controlling a single metabolic reaction. Somehow, this protein appeared to influence the body's ability to use energy, store fat, and sustain physical activity.
That raised an intriguing question: How could disabling one protein produce such widespread effects?
To investigate, the researchers turned their attention to mitochondria, the microscopic structures responsible for supplying much of the energy that cells need to function.
Mitochondria are frequently described as the powerhouses of cells because they convert energy from food into a usable form called ATP, or adenosine triphosphate.
ATP acts as a cellular energy currency. Muscles use it to contract, cells need it to grow and repair themselves, and countless biological processes depend on a steady supply.
However, mitochondria are not static structures. They constantly change shape, joining together into larger networks or separating into smaller units.
When mitochondria fuse, they can form interconnected systems that help coordinate energy production. When they divide, the resulting structures may operate differently, altering how efficiently cells produce and consume energy.
Gross's team had previously established that Mitch plays a major role in mitochondrial fusion, the process that allows separate mitochondria to merge.
Without this protein, the mitochondrial network becomes fragmented. Although the cells can still generate energy, they experience changes in energy efficiency and demand that can force them to consume more fuel.
This offered a possible explanation for the unusual metabolism observed in the mice. Instead of conserving energy efficiently, their cells appeared to be operating in a more energy-intensive state.
But would disabling Mitch have a similar effect in human cells?
To answer that question, researchers led by doctoral student Sabita Chourasia used genetic engineering to remove MTCH2 from human cells grown in the laboratory.
The change disrupted the normal structure of their mitochondrial networks. Individual mitochondria became more separated, and the balance between energy production and energy demand shifted.
The cells developed a persistent shortage of readily available energy relative to their needs, even as their mitochondria increased their oxygen-consuming activity.
To compensate, they began consuming more nutrients.
"After deleting Mitch, we examined, every few hours, the effect that had on more than 100 substances taking part in metabolism in human cells," Chourasia explains. "We saw an increase in cellular respiration, the process in which the cell produces energy from nutrients, such as carbohydrates and fats, using oxygen.