GLP-1 medications like Ozempic have proven highly successful in aiding weight loss in recent years, although they come with side effects such as bone and muscle loss. This has driven the search for natural weight management alternatives without negative consequences, with the protein MTCH2, or ‘Mitch,’ emerging as a potential solution.
A study conducted in 2016 revealed that suppressing Mitch production in mouse muscles protected the animals from obesity and enhanced their stamina and endurance. This, along with earlier research on Mitch, inspired a new study spearheaded by scientists at the Weizmann Institute of Science in Israel. The study explored whether similar effects could be observed in humans.
To investigate, researchers eliminated the gene responsible for Mitch production in human cells in laboratory settings. “After deleting Mitch, we examined, every few hours, the effect that had on more than 100 substances taking part in metabolism in human cells,” explains biologist Sabita Chourasia from the Weizmann Institute of Science. “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.”
The analysis offered deeper insights into Mitch’s role, revealing that it impedes the fusion of mitochondria, the cell’s energy engines, making energy processing less efficient. Consequently, cells lacking Mitch are consistently low on energy, driving them to consume substances like carbohydrates, fats, and amino acids more rapidly. This could explain why mice without Mitch do not gain weight.
Furthermore, researchers discovered that cells without Mitch turned to fats as a primary energy source, breaking down fatty components of cell membranes to be used as fuel. “We discovered that deleting Mitch led to a major drop in fats in membranes,” says biologist Atan Gross from the Weizmann Institute of Science. “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.”
Another significant finding was that Mitch absence disrupts fat cell differentiation, the process of cells turning into fat tissue. “The process of fat accumulation requires a large amount of available energy, but in cells without Mitch, there is a shortage of energy,” notes Gross. “In addition, the expression of genes necessary for differentiation is suppressed, and there is a shortage of the substances vital for this process to occur. As a result, differentiation of new fat cells is reduced, along with fat accumulation.”
Although developing actual treatments is still a distant prospect, identifying Mitch’s pivotal role in both fat-burning and fat-accumulating processes positions it as a promising subject for further research. Comprehensive studies are essential to fully grasp Mitch’s impact, as inducing an energy-deprived state in cells could potentially stress tissues and organs, posing risks to any future treatments.
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“Our findings demonstrate that MTCH2 knockout induces a hypermetabolic state, leading to an imbalance in cellular energy flow and activating multiple metabolic pathways to meet the heightened energy utilization and demand,” write the researchers in their published paper. “These results underscore MTCH2’s role as a crucial regulator of cellular energy flow.”
The research has been published in the EMBO Journal.
This article was fact-checked by Rachel Garner and edited by Peter Dockrill. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.
