Brazilian and North American researchers have identified a protein secreted by brown adipose tissue that is capable of communicating with the liver and, thus, promoting weight loss, in addition to improving the control of glucose and lipids in circulation. The finding paves the way for new treatments against chronic diseases linked to body metabolism, such as obesity and type 2 diabetes.
The research is part of the postdoctoral work of physical educator Carlos Henrique Grossi Sponton, carried out with support from Fapesp at the University of California in San Francisco (United States), and represents a milestone in scientific knowledge about brown fat and its importance for health. . For this reason, it was on the cover of the latest edition of the Embo Reports periodical. Carlos Sponton is a professor at the postgraduate program in Functional and Molecular Biology at the Biology Institute at Unicamp and a researcher at the Obesity and Comorbidities Research Center (OCRC) at Fapesp.
In 2009, this type of adipose tissue, which is responsible for the production of body heat in human newborns, was also identified in adults. “It was a discovery that attracted a lot of interest, because, as it is thermogenic, that is, it generates heat, it consumes more calories”, comments Sponton.
In other words, as it would increase energy expenditure, it could facilitate weight loss. More recently, studies have shown that, just like white fat, which releases hormones, brown adipose tissue also releases molecules with a regulatory role in the body, in addition to heat production.
The interference is possible thanks to batokines – a fusion of the terms BAT (from brown adipose tissue) and cytokines. “They are molecules secreted by brown adipose tissue that have an action similar to that of hormones, communicating with other organs”, points out Sponton. They were the main objects of his work, which included the participation of North American and Japanese scientists.
PLTP batokine and its effect on energy metabolism
In the first step, the researchers compared the molecular profile of brown and white adipose tissue cells extracted from humans. “We identified the proteins that were most expressed in brown tissue, which means that this tissue secreted greater amounts of these proteins,” explains Sponton.
After confirming the greater secretion of these proteins by brown tissue, they employed a genetic engineering strategy (using a viral vector) to test the function of each of these proteins in obese mice. After a series of tests, a protein known as PLTP (an acronym for phospholipid transfer protein) caught the attention of researchers.
“This protein was already known to act on the cardiovascular system, regulating lipid levels in the circulation and altering the structure of some lipoproteins, such as HDL”, explains Sponton. In the experiment, the idea was to verify whether PLTP could alter energy metabolism.
The viral vector, genetically modified to contain the “recipe” for producing PLTP, reaches the liver, the main target of the vector, and its cells transcribe the genetic information. Thus, they begin to release PLTP into the mice's circulation. The increase in circulating levels of this molecule led to important changes in animals.
“The metabolic changes promoted cause part of the lipids that are in peripheral tissues to return to the liver, the so-called reverse transport”, explains Sponton. “The organ processes the excess and, as a result, secretes bile acids,” he adds.
The secretion of bile acids is nothing new; it is a well-known physiological process. The curious thing is that the researchers noticed that the secretion seems to stimulate the functioning of brown adipose tissue. “It starts to generate more heat and, therefore, capture more glucose to have energy for thermogenesis”, points out Sponton.
As the fact that it is more active also means that it is secreting more proteins, including PLTP, the finding indicates a virtuous circle. “In short, the target of this molecule is the brown adipose tissue itself”, comments the scientist.
The mechanism of communication between brown adipose tissue and the liver through PLTP led to increased energy expenditure and, consequently, weight loss and a reduction in body fat in the rodents studied.
Furthermore, they began to have finer control of blood glucose levels and circulating lipids, such as cholesterol and other less known ones, such as sphingolipids and phospholipids.
Possibilities for the future
If the results continue to be encouraging, the expectation is that PLTP can treat diseases where lipid metabolism, glucose metabolism or weight are altered, such as metabolic syndrome, type 2 diabetes or obesity. “The study was a first step, where we were able to learn a little more about the function of the protein, now we will bring it to the physiological context, that is, discuss the possible applications in humans”, says Sponton.
The idea is not to do as in animal studies, in which genetic engineering was used to instruct the body itself to manufacture the molecule, but rather to deliver the protein ready to perform its functions. This way, it will be possible to control dose and quantity. “Insulin, which is also a protein, uses the same reasoning”, points out Sponton.
Today the best-known way to activate brown fat is through exposure to cold. “Some studies show that there are pharmacological agents that act on beta-adrenergic receptors and could stimulate this tissue”, says Sponton.
Their finding is another piece in the puzzle to understand the effects of brown fat on the body and how to replicate them.
Read the article The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT–liver communication
original article published on the Agência Fapesp website.
