“When we are cold, our brain sends a signal via nerves to brown adipose tissue,” says Professor of Endocrinology Patrick Rensen. “This signal activates brown fat cells, which in turn burn sugar and fat molecules from the blood. This is not only CO2 free that is exhaled, but also heat that warms our body.” Rensen and colleagues have now discovered which ‘button’ on the brown fat cells is turned on by the signal from the brain.
Activating brown fat as a treatment?
That is the beta-2 receptor, the researchers write Cell Reports Medicine. “With this knowledge we can make new stimulators that activate brown fat. In theory, this approach can counteract type 2 diabetes and cardiovascular disease because activation of brown fat by cold not only reduces body fat, but also the amount of glucose and cholesterol in the blood,” says Rensen.
Research in humans
Rensen and colleagues previously showed that stimulation of the beta-3 receptor in mice activates brown fat, so that the mice not only lost body fat but also developed less arteriosclerosis. Human brown fat cells were found to have hardly any beta-3 receptor. Stimulation of the beta-2 receptor did appear to activate brown fat cells in the laboratory. Now the researchers have actually demonstrated this in humans.
“We administered salbutamol to 10 volunteers. This is a specific simulator of the beta-2 receptor. It was found to greatly increase the uptake of radiolabeled sugar by brown fat, unless the receptor was blocked. We have demonstrated this with PET-CT scans in collaboration with the Radiology department,” says Rensen.
Prevent side effects
Ultimately, Rensen hopes to treat people with a high risk of type 2 diabetes and/or cardiovascular disease with beta-2 receptor stimulators. But before that happens, the researchers still have a lot of work to do. Rensen: “The first step will be to find a substance that only switches on this receptor on brown fat cells.” The beta-2 receptor is also present on other tissues in our body. “So we first have to find a way to target such stimulators very specifically at brown fat. That way we can prevent side effects of these stimulators elsewhere in the body.”
