A protein secreted by body’s fat help lose weight. Researchers have identified a substance capable of promoting weight loss and improving the control of glucose and circulating lipids.
Brazilian and North American researchers have identified a protein secreted by brown adipose tissue that can communicate with the liver and, thus, favour weight loss, in addition to improving the control of glucose and circulating lipids.
The finding covers the way for new treatments against chronic diseases linked to body metabolisms, such as obesity and type 2 diabetes.
The research is part of the postdoctoral research by physical educator Carlos Henrique Grossi Sponton, carried out with support from FAPESP at the University of California at San Francisco (United States), and represents a milestone in scientific knowledge about brown fat and its importance for health.
In 2009, this type of fatty tissue responsible for producing 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, consumes more calories.”
That is, as it would increase energy expenditure, it could facilitate weight loss. More recently, studies have shown that, like white fat, which releases hormones, brown adipose tissue also releases molecules with a regulatory role in the body and the production of heat.
Interference is possible thanks to batoquines – the fusion of BAT (brown adipose tissue) and cytokines. “They are molecules secreted by the brown adipose tissue that has an action similar to that of hormones, communicating with other organs”, points out Sponton. They were the main objects of his work, which counted on American and Japanese scientists’ participation.
PLTP batoquine and its effect on energy metabolism
In the first stage, 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 the brown tissue, which means that this tissue secreted greater amounts of these proteins,” explains Sponton.
After confirming the increased secretion of these proteins by brown tissue, they employed a genetic engineering strategy (using a viral vector) to test each of these proteins’ function in obese mice. After a series of tests, a protein, known as PLTP (phospholipid transfer protein), caught the researchers’ attention.
“This protein was already known to act on the cardiovascular system, regulating the levels of lipids in the circulation and altering the structure of some lipoproteins, such as HDL”, explains Sponton. In the experiment, the idea was to see if PLTP could alter energy metabolism.
The viral vector, genetically modified to contain the PLTP production “recipe”, reaches the liver, the vector’s primary target, and its cells transcribe genetic information. Thus, they begin to release PLTP in the circulation of mice. The increased levels in the circulation of this molecule led to essential changes in animals.
“The metabolic changes promoted cause part of the lipids that are in the peripheral tissues to return to the liver, the so-called reverse transport”, explains Sponton. “The organ processes 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 the brown adipose tissue. “It starts to generate more heat and, therefore, capture more glucose to have the energy for thermogenesis”, points out Sponton.
As being more active also means that you are 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 communication mechanism between brown adipose tissue and the liver through PLTP led to increased energy expenditure and, consequently, to weight loss and reduction of body fat in the studied rodents.
Besides, they began to have adequate control of blood glucose levels and circulating lipids, such as cholesterol and other lesser-known ones, such as sphingolipids and phospholipids.
Possibilities for the future
If the results remain encouraging, the expectation is that PLTP can treat diseases where the metabolic lipid, glucose or weight changes, such as metabolic syndrome, type 2 diabetes or obesity. “The study was a first step, where we could learn a little more about the function of the protein, now we are going to bring it into the physiological context, that is, discuss the possible applications in humans”, says Sponton.
The idea is not to do as in animal studies. Genetic engineering was used to instruct the body itself to manufacture the molecule and deliver the protein already ready to perform its functions. Thus, it will be possible to control the 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.