A team of researchers led by Guadalupe Sabiofrom the National Cancer Research Center (CNIO), and Cintia Folgueirafrom the CNIO and the National Center for Cardiovascular Research (CNIC), has discovered a new way by which a type of body fat called brown or brown is burned to generate heat in mice.
The study, published in Nature Communicationsreveals a central role in this mechanism of a protein called MCJ, which points to the possibility of regulating its function to fight obesity, a disease that affects 650 million people and is associated with metabolic or cardiovascular disorders and cancer. .
The fat in our body stores energy, the classic calories. This is a task of the so-called white adipose tissue, the normal fat that we carry under the skin; But most mammals, with a few exceptions like pigs, have a second type of fat called brown fat that is burned to keep us warm in response to the cold.
Thus, white fat stores calories, while brown fat burns them. This second is abundant in babies and in the past it used to be believed that it was almost non-existent in adults, but the discovery that it is more present than previously thought has made this tissue the target of numerous anti-obesity research.
The brown or brown color of this type of fat is due to its abundance in mitochondria, organelles present in almost all of our cells that are responsible for producing metabolic energy through the oxygen we inhale when breathing. And, in adipose cells, it is precisely the mitochondria that harbor the ‘fat-burning’ secret of brown fat: thanks to the presence of a special type of protein called thermogenin or UCP1, your mitochondria can burn fat to produce heat, which It helps us warm-blooded animals fight against the cold.
Mitochondria that think they are cold
UCP1 is today in the focus of scientists due to the possibility of regulating its functioning to combat obesity. But recent research has revealed that this is not brown fat’s only mechanism for generating heat. Sabio, Folgueira and their collaborators have discovered one of these new processes, independent of UCP1 and controlled by a protein called MCJ that had previously been identified as a repressor of mitochondrial function in tissues such as the liver; MCJ cancellation accelerates metabolism.
The changes in MCJ related to obesity tell us that in humans the functioning may be the same.
Guadalupe Sabio
— CNIO researcher
Recently, the Interorgan Interaction Group in Metabolic Diseases led by Guadalupe Sabio at the CNIO, together with other collaborators, has shown that the absence of MCJ protects against cardiac risk caused by lack of oxygen. The clue to its intervention in obesity through adipose tissue came from observing the levels of MCJ in the subcutaneous fat of human samples.
As Sabio explains to SINC, “the degree of MCJ activation in each person is related to their metabolic health.” Although brown fat is a minority in the body, subcutaneous fat, which makes up 90% of the total, also contains a third type called beige that behaves in a similar way to brown fat.
When Sabio, Folgueira and their collaborators eliminated MCJ in obese mice, they found that the animals lost weight and generated more heat, replicating previous observations that activation of brown fat protects against obesity and metabolic diseases. By simply transplanting fat without MCJ into obese mice, they achieved weight reduction. “The mitochondria were eating fat and glucose, burning everything that came to them,” summarizes Sabio. In addition, the researchers discovered that the mitochondria changed shape towards a rounded structure, typical when brown fat reacts to cold. By eliminating MCJ, “mitochondria believe they are cold when in reality they are not.”
Lose MCJ to lose weight
In this way, MCJ emerges as a new and promising therapeutic target in the fight against obesity, declared by the World Health Organization as a serious global public health problem that reaches pandemic proportions. But on the path from animal experiments to clinical therapy there are two main big challenges: first, whether the results are applicable to us. Sabio bets that this is the case: “the changes in MCJ related to obesity tell us that in humans the functioning may be the same.”
The second major challenge is to find a way to neutralize the function of MCJ so that this does not cause harmful side effects. This protein is present in other tissues, and the varied missions of metabolic regulators in different organs mean that alteration of any of them can often affect other functions. However, Sabio points out, what is already known about MCJ suggests that its elimination is also beneficial at least for the liver and heart.
In the case of the mice in the study, to eliminate MCJ the researchers have used a type of harmless and modified virus called adeno-associated, which is used in gene therapies, but Sabio believes that perhaps the most appropriate way to silence MCJ in human fat It could be through the use of nanoparticles that specifically target adipose tissue; “This would concentrate the effect where it matters to maximize its action and not dilute it.” In any case, the researcher concludes, “discovering new mechanisms of heat production in brown fat is one of the most interesting targets in the study of obesity.”
#discover #fat #burning #mechanism #opens #ways #treat #obesity
