Turning Off a Protein Called ‘Mitch’ Made Mice Virtually Immune to Obesity. Scientists Just Tested It In Human Cells

Scientists found a cellular switch that raises energy use and blocks new fat cells.

Weight-loss drugs like Ozempic and Wegovy have changed obesity care. But the rapid, almost effortless weight loss they can produce often includes some lean mass, including muscle. This leaves researchers a harder question to tackle for the next generation of weight-loss drugs: how do we reduce excess fat while preserving strength, function, and metabolic health?

A 2025 study points to a protein with a weirdly appropriate nickname: Mitch. In human cells, disabling the protein, formally called MTCH2, pushed cells to burn more fuel and made it harder for new fat cells to form. The work is early and far from a treatment, but it offers a clearer view of why the body stores energy so efficiently, and how that process might be steered.

Unusually Fit Mice

The story began with mice.

Several years ago, Prof. Atan Gross of the Weizmann Institute of Science and his colleagues silenced MTCH2 in mouse muscle. The results were very surprising. The rodents seemed like they could grow obese no matter how much food they ate. They also grew more oxygen-hungry muscle fibers and performed better in physical stress tests. Their heart function improved, too.

This posed a puzzle. How could removing one protein protect against obesity and improve endurance?

The answer led the team to mitochondria, the tiny structures inside cells that turn food into usable energy. Cells draw energy from nutrients such as sugars and fats, but they have to convert it into a chemical form the cell can spend.

Mitochondria are not fixed in place. They merge, split and rearrange themselves as a cell’s needs change. When they form larger connected networks, they tend to produce energy more efficiently. When they remain broken into smaller pieces, the cell gets less energy from the same fuel.

MTCH2 helps mitochondria stay connected. When the researchers removed the protein, that network fell apart — but the cells did not shut down. Instead, they compensated by burning through more sugars, fats and amino acids to meet their energy needs.

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In the new study, led by doctoral student Sabita Chourasia, researchers used genetic engineering to remove MTCH2 from human cells grown in the lab.

“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 said in a statement. “We saw an increase in cellular respiration, the process in which the cell produces energy from nutrients, such as carbohydrates and fats, using oxygen.”

An Energy-Stressed State

The MTCH2-free cells took up more glucose, showed higher oxygen consumption, and burned through amino acids, carbohydrates, and fats. In the study’s terms, the cells entered a hypermetabolic state—they needed more energy and used more raw material to get it.

Typical cells in the experiments leaned more on carbohydrates and proteins. Cells without MTCH2 depended more heavily on fatty acids. They also appeared to pull fat-related molecules from cell membranes and reroute them toward energy production.

“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 fate of fat” captures the study’s broader claim. MTCH2 seems to influence whether cells preserve fat for building and storage or burn it to meet metabolic demand.

The team also tested preadipocytes, immature cells that can grow into fat-storing cells. Fat accumulation depends on more than the storage capacity of existing fat cells. It also depends on whether precursor cells can mature into new adipocytes. To make that transition, the cells need energy, raw materials to build membranes, and a genetic program that pushes them toward a fat-storing identity.

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When MTCH2 was removed, that process largely stalled. The precursor cells struggled to build new fats, showed weaker activity in genes needed for fat-cell development and produced far fewer lipid droplets, the small fat-filled structures found in mature fat cells. Instead of entering a building-and-storing mode, the cells appeared trapped in an energy-stressed state.

Can We Just Turn Mitch Off?

For now, we can’t simply turn off MTCH2 in people.

The experiments took place in human cells, not human bodies. Moreover, MTCH2 also has other roles, including in cell death, mitochondrial behavior, and development. The study itself notes that losing MTCH2 disrupts energy flow across several pathways and can create a catabolic, oxidized cellular environment—useful for studying fat burning, but potentially stressful if applied carelessly in living tissue.

The caution resonates in today’s age of GLP-1 drugs, including Ozempic and related medications. These drugs can produce major weight loss, but some patients also lose muscle. A future obesity treatment would ideally reduce excess fat while preserving strength and metabolic health.

The clearest message from the study is not that MTCH2 is ready to become a drug target, but that fat storage and energy use are tied to the same cellular machinery. When Mitch disappeared, human cells burned more fuel and lost some of their ability to become fat cells. That double effect makes the protein a compelling lead for obesity research. It also sets a high bar: any future therapy would have to shift metabolism toward fat use without pushing cells into damaging energy stress.

The study was published in the EMBO Journal.