Losing Weight Without Losing Muscle Is a Challenge for Drugs Like Ozempic. The Solution May Lie in This Protein

It’s not uncommon to hear about encouraging scientific breakthroughs in mice. However, these experiments often raise the question of whether the findings can be applied to humans. While this isn’t always true, there are notable exceptions.

Mitch. A recent study published in the EMBO Journal shows that suppressing the expression of a simple protein in our muscles can lead to weight loss without endangering muscle mass. This protein is known as Mitochondrial Carrier Homolog 2 (MTCH2), but it’s been nicknamed “Mitch.”

Researchers analyzing this protein and its corresponding gene have revealed that deleting it in human cells makes them less energy-efficient. More significantly, this silencing causes cells to stop prioritizing carbohydrates as their primary energy source and instead preferentially use body fat.

Different fuels. Cells need energy, and millions of years of evolution have led to the development of biological mechanisms that allow humans to maintain a reserve of calories. Reserves provide energy for our cells during times of greater scarcity.

These mechanisms enable cells to use different fuel sources in different situations. Carbohydrates and fats are the primary fuels we consume, but our bodies can also use proteins as an alternative energy source. However, relying on protein can lead to a loss of muscle mass when attempting to burn fat. This is what happens with contemporary treatments like Ozempic.

From mice to mitochondria. According to the research team, the study builds on previous experiments conducted with mice. Previous studies showed a “general improvement” in body composition, specifically through protection against obesity and an increase in muscle fiber development. These changes were accompanied by heightened oxygen consumption and improved endurance.

However, researchers faced a critical question: Could they “inoculate” the body against obesity by silencing the expression of a specific protein without negatively impacting muscle mass? To explore this, the team focused on the role of mitochondria, organelles responsible for providing energy to cells.

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The key factor is the Mitch protein, which plays a crucial role in the fusion of mitochondria. This fusion enhances the efficiency of organelles. When the protein is silenced, organelles lose their ability to undergo this fusion. The result is a reduced efficiency and an increased demand for energy resources from our bodies. The next step was to determine whether this effect also occurs in human cells.

Less efficiency, more consumption. Researchers found that silencing a specific protein in human cells caused the mitochondrial network to unravel, leading to a significant drop in energy efficiency. As a result, cells entered a “permanent state of energy deprivation.” Moreover, the team discovered that this change prompted cells to prioritize fats as their primary energy source instead of carbohydrates.

“After deleting Mitch, we examined, every few hours, the effect that had on more than 100 substances taking part in metabolism in human cells,” co-author Sabita Chourasia said in a press release. He added, “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.”

An intermediate step. The study represents an important step forward in the lengthy process of translating initial findings from animal models into the development of a weight loss treatment.

The research team plans to conduct further studies to clarify new aspects of Mitch’s role in body fat accumulation. Notably, since women generally have higher levels of this protein, this may help researchers determine whether Mitch is also involved in fat cell differentiation.

Image | Marvin Radke

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