Scientists Discover Protein Switch That Burns Fat and Prevents New Fat Cells

What if losing weight meant burning more fat without sacrificing muscle? Scientists at the Weizmann Institute of Science have identified a protein that could one day make that possible. Their study, published in the EMBO Journal, found that disabling a protein called MTCH2, nicknamed "Mitch," significantly boosts fat burning while preventing the formation of new fat cells.

The discovery builds on earlier mouse studies, where animals lacking Mitch in their muscles became leaner, developed greater endurance, gained more muscle fibers, and were highly resistant to obesity. To understand why, researchers examined the protein's role in mitochondria—the energy-producing structures inside cells.

Using genetic engineering, the team removed Mitch from human cells. Without the protein, mitochondria broke into smaller units, making energy production less efficient. To compensate, the cells increased their consumption of fats, carbohydrates, and amino acids to meet their energy demands.

Researchers observed a major shift in metabolism. Unlike normal cells, which rely primarily on carbohydrates and proteins, Mitch-deficient cells used fat as their main fuel source. They also found that fats stored in cell membranes were broken down and used for energy, suggesting that Mitch plays a key role in determining whether fat is stored or burned.

The study revealed another important finding. When Mitch was removed from fat progenitor cells—immature cells that develop into fat-storing cells—the process of fat-cell formation was significantly disrupted. The cells lacked sufficient energy and failed to activate genes needed for differentiation, resulting in reduced fat accumulation.

Although the findings are based on laboratory studies and are still far from clinical use, they highlight a promising new target for obesity treatment. By increasing energy expenditure, enhancing fat burning, and limiting new fat-cell formation, therapies targeting MTCH2 could potentially complement existing weight-loss medications while helping preserve muscle mass. Further research is needed before this approach can be tested in humans.

REFERENCE: Sabita Chourasia, Christopher Petucci, Clarissa Shoffler, Dina Abbasian, Hu Wang, Xianlin Han, Ehud Sivan, Alexander Brandis, Tevie Mehlman, Sergey Malitsky, Maxim Itkin, Ayala Sharp, Ron Rotkopf, Bareket Dassa, Limor Regev, Yehudit Zaltsman, Atan Gross. MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis. The EMBO Journal, 2025; 44 (4): 1007 DOI: 10.1038/s44318-024-00335-7