Obesity and being overweight: meet the Mitch protein – switching it off means fat is ‘burned’ first

Some might refer to the ‘pineapple effect’, recalling the old popular (non-scientific) saying that regards this fruit as a sort of natural ‘fat-burner’. But sticking to the scientific evidence, a new avenue for treating obesity is opening up, which could complement the medicines currently available in the future. The focus is on deactivating the MTCH2 protein, which has been nicknamed – as if it were a friend – ‘Mitch’. This approach, in fact, achieves a twofold result: it significantly accelerates fat burning and blocks the formation of new fat cells, thereby targeting two key factors in weight control. As if that were not enough, compared with existing medicines, by targeting this particular biological mechanism, there is hope of avoiding the loss of muscle mass often experienced by those undergoing current treatments. Hopes for a scientifically proven ‘pineapple’ effect are fuelled by research carried out by experts at the Weizmann Institute of Science (in collaboration with researchers from the University of Pennsylvania and the University of Texas at San Antonio), led by Sabita Chourasia and Atan Gross. The study was published in the EMBO Journal. 

Mitch’s work focuses on regulating the activity of mitochondria, which generate the energy cells need to function and play a central role in metabolism – the set of chemical processes that convert food into usable energy. However, the way mitochondria are ‘organised’ can reveal more about energy management. Sometimes mitochondria merge into large, interconnected networks that generate energy most efficiently. In other circumstances, however, they form smaller, less efficient units. In such cases, the cells compensate by consuming greater quantities of fuel, primarily fats and carbohydrates, including fats, carbohydrates and proteins. It is within this invisible mechanism that Mitch comes into play, helping to regulate the process by controlling mitochondrial fusion. Having verified these steps in animals, the experts wanted to see what happens in humans.

In the research just presented, Mitch was effectively removed from human cells using genetic engineering techniques. This simple action disrupted the mitochondria’s operational network, making energy production less efficient and forcing the cells to operate in a constant state of energy deficiency. Although one might think this is not a good thing, if the aim is to lose weight, it is actually a very positive outcome, as cells that struggle to produce energy have to burn more fuel to meet their own needs. ‘After eliminating Mitch, we examined, every few hours, the effect this had on over 100 substances involved in human cell metabolism,’ the Chourasia Centre stated in a press release. “We observed an increase in cellular respiration – the process by which cells produce energy from nutrients, such as carbohydrates and fats, using oxygen. This explains the increase in muscle endurance observed in previous experiments on mice.”

Final summary. Cells modified to knock out Mitch increased their utilisation of available fuel sources, with greater breakdown of fats, carbohydrates and amino acids. Not only that: whilst normal cells generally rely more heavily on carbohydrates and proteins, those lacking Mitch preferentially chose lipids as their primary source of energy. Not only that: there is another positive effect linked to the removal of the protein, which stems from studies on fat cells that originate from precursor cells known as progenitor cells. Under the right conditions, these immature cells accumulate fat and develop into mature cells that store fat through a process called differentiation. When the researchers removed Mitch from the progenitor cells, this transformation became much more difficult. In short: the cells lacking Mitch not only burnt more fat, but were also less capable of creating new fat cells.

We are still at the cellular level, not at the level of the human organism. But these results offer hope that, in the future, we may be able to take a new direction in obesity research, based on the possibility of using Mitch to influence both energy expenditure and fat accumulation. All this comes with a significant advantage over current approaches to weight-loss therapies: the preservation of muscle mass and the mitigation of the risk of sarcopenia, which is linked precisely to a lack of lean muscle tissue. ‘This research opens up a very interesting prospect because it identifies a new mechanism by which cells regulate energy expenditure and fat accumulation,’ explains Livia Pisciotta, full professor and Director of the School of Medical Specialisation in Food Science at the University of Genoa. “The most innovative aspect is the theoretical possibility of increasing energy expenditure and limiting the formation of new adipose tissue whilst, at the same time, preserving muscle mass – one of the main limitations of current obesity treatments.”