Scientists Discover 'Mitch' — A Protein Switch That Turns Off Fat Storage and Boosts Fat Burning

For decades, rising availability of ultra-processed foods and increasingly sedentary lifestyles have helped fuel a global obesity crisis: an estimated 40 percent of U.S. adults now live with obesity. While diet and exercise remain central to weight management, researchers are also hunting biological targets that could help shift the body from storing fat to burning it.

A new study led by scientists at the Weizmann Institute of Science and published in the EMBO Journal examines a protein called MTCH2 (nicknamed "Mitch"). MTCH2 is involved in apoptosis, mitochondrial function, and metabolic regulation. Over the past decade senior author Atan Gross and colleagues showed in mice that lowering MTCH2 affects muscle metabolism and whole-body energy balance. The new paper reports parallel results in human cells and sheds light on how MTCH2 influences whether cells store or burn fat.

What the Study Found

The team—including lead author Sabita Chourasia—used human cells to test how reduced MTCH2 expression changes cellular energy use. They observed that lowering MTCH2 led to:

• Reduced lipid content in cellular membranes and a release of fatty molecules that cells then used for energy.
• An increase in cellular respiration (the oxygen-dependent process that converts nutrients into usable energy), even though overall cellular energy production measurements indicated altered energy homeostasis.
• Decreased conversion of progenitor cells into mature fat (adipocyte) cells, suggesting a role for MTCH2 in adipogenesis.

"We discovered that deleting Mitch led to a major drop in fats in membranes," Gross said. "At the same time, we saw an increase in fatty substances used to produce energy... Mitch determines the fate of fat in human cells."

Previous mouse experiments published in 2016 indicated that MTCH2 is a "pivotal regulator of muscle metabolism and whole-body energy homeostasis." The new human-cell data reproduce key aspects of those findings: MTCH2 suppression appears to push cells away from storing lipids and toward mobilizing them for fuel.

Biological and Clinical Implications

The researchers note that higher MTCH2 levels have been observed in women with obesity, which supports the idea that this protein contributes to how cells differentiate into fat-storing adipocytes. From an evolutionary perspective, MTCH2 may once have helped early humans survive periods of scarcity by promoting fat storage. In a modern environment of calorie abundance, that same mechanism could be maladaptive.

Importantly, these results come from cellular and preclinical studies. While MTCH2 represents a promising target, developing safe and effective therapies will require extensive additional research in animals and humans, along with careful evaluation of potential side effects because MTCH2 also participates in critical processes such as cell death and mitochondrial function.

Takeaway

Suppressing MTCH2 shifts cellular metabolism away from lipid accumulation and toward increased lipid use for energy, and it reduces the formation of new fat cells in laboratory experiments. The protein is a potential candidate for future obesity and metabolic-disease therapies, but clinical translation will take time and further study.