Scientists discover protein switch that makes human cells burn fat and block fat formation

Disabling the MTCH2 protein, nicknamed 'Mitch', could open a new path to fighting obesity by targeting how cells use energy rather than appetite.

By LineZotpaper AI staff

Published24 October 2026

Read Time3 min

Researchers at the Weizmann Institute of Science have identified a single protein, MTCH2, that acts as a switch determining whether human cells burn fat or store it. Disabling this protein, nicknamed 'Mitch', increased fat consumption and blocked the formation of new fat cells in laboratory experiments, offering a potential new approach to obesity treatment that targets metabolism rather than appetite.

Scientists have discovered that disabling a protein called MTCH2 makes human cells burn more fat and interferes with the formation of new fat cells, raising the possibility of a different approach to treating obesity.

The research, led by Professor Atan Gross and doctoral student Sabita Chourasia at the Weizmann Institute, builds on earlier experiments in mice in which switching off the protein in muscle tissue increased energy expenditure, improved endurance, and protected the animals from diet-related obesity. Those findings prompted the team to investigate the mechanism in human cells.

Using genetic engineering to remove MTCH2 from human cells grown in the laboratory, the researchers found that the change disrupted the normal structure of mitochondrial networks. Mitochondria, often described as the powerhouses of cells, convert energy from food into a usable form. Without MTCH2, the cells developed a persistent shortage of readily available energy relative to their needs, even as their mitochondria increased oxygen-consuming activity. To compensate, the cells began consuming more nutrients, including fats, carbohydrates, and amino acids.

"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 explained. "We saw an increase in cellular respiration, the process in which the cell produces energy from nutrients, such as carbohydrates and fats, using oxygen. This explains the increase in muscular endurance in previous experiments using mice."

Fat metabolism was particularly revealing. Rather than relying on their usual mix of energy sources, the altered cells increased their use of fatty acids for fuel. "We discovered that deleting Mitch led to a major drop in fats in membranes," Gross explained. "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 findings, published in The EMBO Journal in January 2025, suggest that manipulating MTCH2 could eventually offer a way to influence both fat burning and fat accumulation. Additional research published later that year provided further evidence of the protein's importance in regulating body fat and metabolism.

The discovery comes amid growing interest in obesity treatments that do more than suppress appetite. Widely used drugs such as semaglutide and tirzepatide help patients lose weight by influencing appetite, but weight loss can also include a reduction in lean body mass. 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 weight-loss medications, a proportion also seen with lifestyle interventions. Adding resistance training helped preserve more lean tissue.

Professor Gross and his team hope that targeting MTCH2 could provide a way to reduce body fat while protecting muscle, though human trials of any potential treatment remain years away.

Analysis

Why This Matters

Obesity treatments that target appetite, such as semaglutide and tirzepatide, can lead to loss of lean muscle mass along with fat. A metabolism-focused approach could preserve muscle while reducing fat.
The discovery identifies a single protein that controls both fat burning and fat cell formation, potentially offering a more targeted treatment with fewer side effects.
If the mechanism can be replicated in humans through a drug, it could provide an alternative for patients who do not respond well to existing weight-loss medications.

Background

Over the past decade, drugs like semaglutide and tirzepatide have transformed obesity treatment by reducing appetite. However, losing weight often means losing muscle as well as fat. A 2026 analysis of 20 clinical trials found that lean mass made up a significant portion of weight lost with these drugs. Preserving muscle is important for strength, mobility, and metabolic health. Scientists have been searching for ways to reduce body fat specifically. The Weizmann Institute team arrived at a possible avenue through an unexpected discovery involving the MTCH2 protein, originally studied for its role in mitochondrial fusion.

What to Watch

Whether researchers can develop a drug that safely and selectively inhibits MTCH2 in humans.
Clinical trials testing the approach for safety and efficacy in reducing body fat while preserving lean mass.
Further studies to confirm the protein's role in other tissues, such as the liver and brain, to predict potential side effects.

Sources

Scientists discover a hidden switch that burns fat and blocks new fat cells · ScienceDaily

Checked

11 claims in this story checked against 1 source: 8 supported.

Show each claim

SupportedDisabling MTCH2 makes human cells burn more fat.Latest Science News -- ScienceDaily: “The researchers found that cells lacking Mitch consumed more fats, carbohydrates, and amino acids.”
Partly supportedDisabling MTCH2 blocks new fat-cell formation in human cells.Latest Science News -- ScienceDaily: “Importantly, the fat cell differentiation experiments used a mouse-derived cell line, while the detailed analysis of nutrient consumption was conducted in human cells.”
SupportedMTCH2 acts as a switch determining whether human cells burn fat or store it.Latest Science News -- ScienceDaily: “Overall, the results showed that MTCH2 is a powerful regulator of how cells allocate nutrients between energy production and other biological needs.”
SupportedThe research suggests that manipulating MTCH2 could offer a different approach to treating obesity by changing how cells use energy rather than suppressing appetite.Latest Science News -- ScienceDaily: “That combination raises the possibility of developing treatments that change how the body handles energy, potentially complementing medications that primarily work by reducing appetite.”
SupportedDeleting Mitch increased cellular respiration, which Chourasia said explained increased muscular endurance in previous mouse experiments.Latest Science News -- ScienceDaily: “We saw an increase in cellular respiration, the process in which the cell produces energy from nutrients, such as carbohydrates and fats, using oxygen. This explains the increase in muscular endurance in previous experiments using mice.”
SupportedGross said deleting Mitch caused a major drop in fats in membranes and that fat was broken down from the membrane to be used as fuel.Latest Science News -- ScienceDaily: “We discovered that deleting Mitch led to a major drop in fats in membranes. 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.”
SupportedEarlier mouse experiments found that switching off MTCH2 in muscle increased energy expenditure, improved endurance and protected the animals from diet-related obesity.Latest Science News -- ScienceDaily: “The discovery builds on earlier experiments in mice, in which switching off Mitch in muscle tissue increased energy expenditure, improved endurance, and protected the animals from diet-related obesity.”
SupportedA 2026 analysis of 20 clinical trials with 15,782 participants found that lean mass made up approximately 25% to 39% of weight lost with several weight-loss medications.Latest Science News -- ScienceDaily: “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.”
SupportedThe analysis found comparable proportional lean-mass losses with lifestyle interventions, and resistance training helped preserve more lean tissue.Latest Science News -- ScienceDaily: “Importantly, the researchers found that comparable proportional losses also occurred with lifestyle interventions, while adding resistance training helped preserve more lean tissue.”
Not in the sourcesHuman trials of a potential MTCH2 treatment remain years away.Latest Science News -- ScienceDaily: “Scientists have not yet demonstrated that inhibiting MTCH2 produces safe, sustained weight loss in humans.”
Not in the sourcesGross and his team hope that targeting MTCH2 could reduce body fat while protecting muscle.Latest Science News -- ScienceDaily: “Researchers will need to determine whether MTCH2 can be targeted safely, which tissues would benefit most, and whether reducing its activity would preserve muscle health while promoting fat loss.”