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Scientists from the Spanish national cancer and cardiovascular research centres (CNIO) and (CNIC) have discovered a way to make the body burn more fat, transforming it into heat. This in turn opens up the possibility of designing new therapies in the fight against obesity, a serious pathology that is constantly on the rise throughout the developed world and which affects more than 16% of the adult population in Spain and over 10% of children and adolescents.
The discoveries of the scientific teams led by Guadalupe Sabio and Cintia Folgueira not only offer hope for minimising a disease that affects some 650 million people worldwide, but could also help protect patients from other obesity-related diseases, such as diabetes or excess cholesterol in the bloodstream. Obesity, in general, is a risk factor for developing multiple metabolic pathologies, but also cardiovascular diseases and cancers.
The two teams have identified a mechanism, controlled by a protein called MCJ, which is found in the mitochondria (the energy centres of cells) of brown fat in the human body. They have shown that when this protein is removed in obese mice, these rodents generate more body heat, which causes them to increase their energy consumption, thereby reducing their fat stores and losing weight.
The research, following the first finding, now seeks to develop a therapy to block this protein in patients with obesity. But to take this step they first need to find out whether the MCJ protein has vital functions in other tissues. In other words, if suppressing it to fight obesity does not cause other secondary damage to the body. At the same time, said Guadalupe Sabio, "we are trying to see if these changes in fat affect tumour growth or cachexia - loss of muscle and fat - which is also sometimes associated with cancer".
There are two types of adipose tissue (fat) in the human body: white and brown. White adipose tissue primarily stores energy, while brown fat is responsible for heat generation or thermogenesis, the process that maintains body temperature and is activated in response to cold or other stimuli.
Obesity is therefore caused either by excessive food intake or inadequate total energy expenditure, or a mixture of both. This is why several studies have shown that activating brown fat protects against obesity and metabolic diseases. "It is thought that obesity could be prevented by getting this fat to expend more energy by generating heat," said Sabio. Therefore, discovering new mechanisms for heat production in brown fat, as his teams have done with the suppression of the MCJ protein, "is one of the most interesting targets in the study of obesity," he said.
For a long time it was thought that brown fat used a single mechanism to generate heat, but we now know that this is not the case. There are several mechanisms. CNIO research has discovered that, when the MCJ protein is eliminated in obese mice, the animals lose weight. What's more, according to the scientists, it was enough to transplant these animals with brown fat without the MCJ protein to reduce their weight.
The Spanish researchers also observed "that animals without MCJ in brown fat are protected against the health problems caused by obesity, such as diabetes or increased blood lipids". They therefore believe that the MCJ protein could also be a new therapeutic target to correct pathologies associated with obesity.
"This protection," explained CNIO researcher Beatriz Cicuéndez, first author of the article, "is due to the activation of a signalling pathway that is essential for adaptation to the stress caused by obesity. This pathway causes an increase in the consumption of fats, sugars and proteins, known as catabolism, to produce heat in brown fat. It is a mechanism that also occurs in people with very active brown fat.
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