MTCH2 уураг нь эсийн өөх тос шатаах болон хуримтлуулах үйл явцыг удирддаг болохыг тогтоожээ

What if one of the keys to fighting obesity lies not in suppressing appetite, but in changing how the body’s cells use energy?

Researchers at the Weizmann Institute of Science have identified a protein called MTCH2, nicknamed “Mitch,” that plays an important role in controlling metabolism. When scientists disabled this protein in laboratory experiments, cells began consuming more fuel, including fats and carbohydrates. They also found that removing Mitch could interfere with the process through which immature cells develop into fat cells.

The discovery builds on earlier experiments in mice, in which switching off Mitch in muscle tissue increased energy expenditure, improved endurance, and protected the animals from diet-related obesity.

The findings, published in The EMBO Journal in January 2025, suggest that manipulating this protein could eventually offer a way to influence both fat burning and fat accumulation. Additional research published later that year has provided further evidence of its importance in regulating body fat and metabolism.

Why Scientists Are Searching for Better Obesity Treatments

Over the past decade, medications designed to promote weight loss have transformed obesity treatment. Drugs such as semaglutide and tirzepatide have helped many patients achieve substantial reductions in body weight, largely by influencing appetite and the body’s responses to food.

But losing weight does not necessarily mean losing only fat.

Weight reduction can also involve a decline in lean body mass, which includes muscle and other tissues. Preserving muscle is especially important because it supports strength, mobility, and metabolic health.

A 2026 analysis of 20 clinical trials involving 15,782 participants found that lean mass accounted for approximately 25% to 39% of the weight lost with several widely used weight-loss medications. Importantly, the researchers found that comparable proportional losses also occurred with lifestyle interventions, while adding resistance training helped preserve more lean tissue.

These concerns have encouraged scientists to investigate ways to reduce body fat while protecting the muscles needed for long-term health.

Professor Atan Gross and his colleagues at the Weizmann Institute arrived at a possible avenue through an unexpected discovery involving Mitch.

Switching Off One Protein Protected Mice From Obesity

In earlier experiments, Gross’s team reduced the activity of MTCH2 in the muscles of mice. The effects were striking.

The genetically modified animals showed increased metabolic activity and were resistant to obesity caused by their diet. Their muscles also developed more fibers with a high capacity for using oxygen, helping improve physical endurance.

The mice performed better in exercise and stress tests and showed improvements in heart function. In addition to resisting excess fat accumulation, they experienced favorable changes in their overall body composition.

The results suggested that Mitch was doing much more than controlling a single metabolic reaction. Somehow, this protein appeared to influence the body’s ability to use energy, store fat, and sustain physical activity.

That raised an intriguing question: How could disabling one protein produce such widespread effects?

To investigate, the researchers turned their attention to mitochondria, the microscopic structures responsible for supplying much of the energy that cells need to function.

The Mitochondria Connection Behind Fat Burning

Mitochondria are frequently described as the powerhouses of cells because they convert energy from food into a usable form called ATP, or adenosine triphosphate.

ATP acts as a cellular energy currency. Muscles use it to contract, cells need it to grow and repair themselves, and countless biological processes depend on a steady supply.

However, mitochondria are not static structures. They constantly change shape, joining together into larger networks or separating into smaller units.

When mitochondria fuse, they can form interconnected systems that help coordinate energy production. When they divide, the resulting structures may operate differently, altering how efficiently cells produce and consume energy.

Gross’s team had previously established that Mitch plays a major role in mitochondrial fusion, the process that allows separate mitochondria to merge.

Without this protein, the mitochondrial network becomes fragmented. Although the cells can still generate energy, they experience changes in energy efficiency and demand that can force them to consume more fuel.

This offered a possible explanation for the unusual metabolism observed in the mice. Instead of conserving energy efficiently, their cells appeared to be operating in a more energy-intensive state.

But would disabling Mitch have a similar effect in human cells?

Human Cells Begin Burning More Fat Without Mitch

To answer that question, researchers led by doctoral student Sabita Chourasia used genetic engineering to remove MTCH2 from human cells grown in the laboratory.

The change disrupted the normal structure of their mitochondrial networks. Individual mitochondria became more separated, and the balance between energy production and energy demand shifted.

The cells developed a persistent shortage of readily available energy relative to their needs, even as their mitochondria increased their oxygen-consuming activity.

To compensate, they began consuming more nutrients.

“After deleting Mitch, we examined, every few hours, the effect that had on more than 100 substances taking part in metabolism in human cells,” Chourasia explains. “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.”

Cellular respiration is the series of chemical reactions that allows cells to extract usable energy from nutrients. Increasing this activity generally requires a greater supply of fuel.

The researchers found that cells lacking Mitch consumed more fats, carbohydrates, and amino acids, the building blocks of proteins.

Fat metabolism was particularly revealing.

Rather than relying on their usual mix of energy sources, the altered cells increased their use of fatty acids for fuel. This indicated that MTCH2 influences not only how much energy cells consume, but also which nutrients they use to meet that demand.

“We discovered that deleting Mitch led to a major drop in fats in membranes,” Gross explains. “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.”

Cell membranes are thin, flexible barriers made largely from fatty molecules called lipids. They protect cells and organize many of their essential functions.

The findings suggested that cells deprived of Mitch were changing how they distributed and used these lipids, drawing on some of their available fatty resources to support increased energy consumption.

Detailed analysis also revealed changes in stored lipids, demonstrating that the effect was more complex than simply eliminating cellular fat. Overall, the results showed that MTCH2 is a powerful regulator of how cells allocate nutrients between energy production and other biological needs.

Blocking the Formation of New Fat Cells

The researchers then investigated whether Mitch also influences how fat cells develop.

This question was particularly interesting because previous studies had found elevated MTCH2 levels in fat tissue from women with obesity.

Fat cells, also known as adipocytes, do not appear fully formed. They develop from immature precursor cells through a process called adipogenesis, or fat cell differentiation.

As these precursor cells mature, they must build new cellular structures, produce fats, and activate genes that allow them to specialize in storing energy.

All of this requires considerable energy and raw materials.

Gross’s team suspected that removing Mitch might disrupt the process by creating an environment in which cells were too busy consuming fuel to build the components needed for fat storage.

Experiments using mouse precursor fat cells supported this idea. When the researchers deleted MTCH2, far fewer cells successfully developed into mature fat cells.

In the published experiments, approximately 80% to 90% of normal precursor cells differentiated within six days, compared with only 5% to 10% of cells lacking MTCH2. The altered cells also accumulated substantially fewer lipid droplets, the structures used to store fat.

“When we deleted Mitch from the progenitor cells, we discovered that the environment created in these cells was not conducive to the synthesis of new fats,” Gross explains. “Reducing the ability to synthesize membranes prevents the cells from growing, developing and reaching the point where differentiation is possible. The process of fat accumulation requires a large amount of available energy, but in cells without Mitch, there is a shortage of energy. 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.”

In other words, disabling Mitch appeared to affect fat metabolism in two distinct ways. It increased the consumption of energy-rich nutrients and interfered with the cellular machinery needed to develop new fat-storing cells.

Importantly, the fat cell differentiation experiments used a mouse-derived cell line, while the detailed analysis of nutrient consumption was conducted in human cells. The combined results suggest a broader role for the protein, but they do not establish that blocking MTCH2 would prevent new fat cells from forming in people.

Follow-Up Research Reveals Another Fat-Burning Mechanism

The importance of MTCH2 became even clearer in research published on October 3, 2025, in Nature Communications.

An international research team, which included Gross and Chourasia, investigated how MTCH2 influences metabolism in fat tissue. By analyzing human and mouse fat samples, studying cultured fat cells, and conducting experiments in genetically modified mice, the scientists identified another mechanism linking this protein to energy expenditure.

They found that MTCH2 helps regulate the movement of fatty acids into mitochondria, where these molecules can be broken down to produce energy.

The process involves an enzyme called carnitine palmitoyltransferase 1, or CPT1. This enzyme acts as an important checkpoint, helping determine how much fat can enter mitochondria for use as fuel.

Normally, CPT1 activity is regulated by a molecule called malonyl-CoA, which signals when cells should limit fatty acid consumption.

The researchers discovered that MTCH2 physically interacts with CPT1 and influences how strongly this regulatory signal affects the enzyme.

Removing MTCH2 altered that control system, allowing mitochondria to increase fatty acid utilization and energy expenditure.

This provided a more detailed molecular explanation for why disabling the protein could encourage cells to burn additional fat.

Mice Burned More Energy Without Eating Less

The follow-up study also produced an especially promising result.

When researchers removed MTCH2 specifically from the fat cells of mice, the animals burned more energy without increasing their physical activity or changing how much food they consumed.

Under a regular diet, the genetically modified mice gained weight at a rate similar to that of normal mice.

However, when the animals were fed a high-fat diet, a difference emerged.

Mice lacking MTCH2 in their fat tissue gained less weight and accumulated less body fat than untreated mice, despite consuming similar amounts of food.

Their lean body mass remained comparable to that of the control animals.

The genetically modified mice also demonstrated improved glucose tolerance, indicating that their bodies were better able to manage blood sugar after receiving glucose. In addition, their cholesterol levels were lower.

These findings strengthened the evidence that MTCH2 influences whole-body metabolism, rather than simply changing the behavior of isolated cells.

The scientists also found that its metabolic effects could occur independently of UCP1, a protein commonly associated with heat production in brown fat. Brown fat is a specialized form of body fat that helps generate heat by burning energy, whereas white fat primarily stores excess energy.

Discovering an additional pathway for increasing energy expenditure could be important because it offers researchers another potential target for treating obesity and related metabolic disorders.

Could This Protein Lead to Better Weight-Loss Treatments?

Together, the findings suggest that MTCH2 may be an important molecular switch linking fat storage, energy consumption, and the development of fat cells.

The original experiments showed that removing the protein could increase nutrient consumption in human cells and interfere with fat cell formation in mouse cells. The later research demonstrated that selectively removing MTCH2 from fat tissue could increase energy expenditure and protect mice against excessive weight gain on a high-fat diet.

That combination raises the possibility of developing treatments that change how the body handles energy, potentially complementing medications that primarily work by reducing appetite.

However, several major questions remain unanswered.

Scientists have not yet demonstrated that inhibiting MTCH2 produces safe, sustained weight loss in humans. The protein also participates in other important biological activities, including mitochondrial regulation and pathways involved in cell survival. Blocking it throughout the body could therefore produce unwanted consequences.

Preventing fat cells from forming is not necessarily beneficial in every situation, either. Healthy fat tissue plays an essential role in storing excess energy, maintaining blood sugar balance, and producing hormones. Disrupting its function could potentially redirect fats into organs where they may cause harm.

Researchers will need to determine whether MTCH2 can be targeted safely, which tissues would benefit most, and whether reducing its activity would preserve muscle health while promoting fat loss.

For now, established strategies such as resistance exercise and adequate protein intake remain important for protecting muscle during weight reduction. A 2026 review of clinical trials found that combining lifestyle changes with resistance training produced a more favorable pattern of lean mass preservation than weight-loss interventions without such exercise.

The research nevertheless points toward a compelling possibility: Rather than focusing exclusively on how much food the body takes in, future obesity treatments might also influence how cells decide whether to burn energy or store it.

And one protein, Mitch, appears to be deeply involved in that decision.

Research Team and Publication Details

The original study, titled “MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis,” was published in The EMBO Journal on January 3, 2025.

The research was led by Sabita Chourasia and Professor Atan Gross at the Weizmann Institute of Science.

Additional contributors included Dr. Christopher Petucci, Clarissa Shoffler, and Dina Abbasian from the University of Pennsylvania in Philadelphia; Hu Wang and Professor Xianlin Han from the University of Texas at San Antonio; Dr. Ehud Sivan, Dr. Alexander Brandis, Tevie Mehlman, Dr. Sergey Malitsky, Dr. Maxim Itkin, Dr. Ayala Sharp, Dr. Ron Rotkopf, and Dr. Bareket Dassa from Weizmann’s Life Sciences Core Facilities Department; and Dr. Limor Regev and Dr. Yehudit Zaltsman from Weizmann’s Immunology and Regenerative Biology Department.

The follow-up study, “MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes,” was published in Nature Communications on October 3, 2025. It involved an international collaboration, including researchers affiliated with ETH Zurich, Weizmann Institute of Science, and other institutions.