Protein tied to fat burning may point to new obesity research path

Researchers at the Weizmann Institute of Science say a protein known as MTCH2 appears to help decide whether cells burn fat or store it. The finding matters because it identifies a possible target for future obesity research, though the work remains at the cell-study stage.

The team reported in The EMBO Journal that removing MTCH2, nicknamed “Mitch,” from human cells changed how the cells produced energy. According to Weizmann, cells without the protein used more oxygen, broke down more fuel and became less able to develop into new fat-storing cells.

The study builds on earlier mouse work by Prof. Atan Gross and colleagues at Weizmann. In those experiments, mice whose muscle tissue lacked Mitch were leaner, had more endurance, showed better performance under physical stress and were resistant to obesity, according to the institute.

How the protein affects cell energy

Weizmann said the new work focused on mitochondria, the structures inside cells that produce usable energy. Gross’s group found that Mitch helps regulate whether mitochondria fuse into larger networks or remain split into smaller units.

According to the researchers, that structure affects how efficiently cells make energy. When mitochondria are less efficient, cells must consume more fuel to meet their energy needs, including fats, carbohydrates and amino acids.

In the new study, doctoral student Sabita Chourasia led experiments using genetic engineering to remove Mitch from human cells. Weizmann said the loss of the protein caused mitochondrial networks to break apart and left cells in a state of energy shortage.

The researchers then tracked more than 100 substances involved in metabolism. Chourasia said the team saw an increase in cellular respiration, the oxygen-using process by which cells generate energy from nutrients such as carbohydrates and fats, which could help explain the endurance effects previously observed in mice.

More fat used as fuel

The Weizmann team said cells lacking Mitch shifted toward greater fat use. Gross said the researchers found a drop in fats in cell membranes alongside a rise in fatty substances being used for energy, indicating that membrane fat was being broken down as fuel.

According to the institute, ordinary cells relied more on carbohydrates and proteins, while cells without Mitch depended more heavily on fat. The researchers said this suggests MTCH2 helps control the fate of fat inside human cells.

The team also tested whether the protein affects adipogenesis, the process by which precursor cells become mature fat cells. Weizmann said earlier studies had found elevated levels of Mitch in women with obesity, prompting the researchers to examine its role in new fat-cell formation.

When the scientists removed Mitch from progenitor cells, those cells had more difficulty becoming fat cells, according to Gross. He said the altered cells lacked the energy, membrane-building capacity, gene activity and other substances needed for normal differentiation and fat accumulation.

Early-stage implications

The findings do not show that blocking MTCH2 would be safe or effective as a treatment in people. Weizmann described the work as a possible new direction for obesity research rather than a therapy ready for use.

The institute said the pathway could interest researchers because current weight-loss medicines can reduce muscle mass as well as body fat. The study involved scientists from the Weizmann Institute of Science, the University of Pennsylvania and the University of Texas at San Antonio.

This story draws on original reporting from ScienceDaily.