Researchers have found that blocking the uptake of a specific hormone in mice prompts the burning of the animal's stores of beige fat, or adipose tissue. The researchers say the discovery of this regulatory mechanism provides a new target for the development of drugs that combat obesity by boosting the burning of stored fat in the human body.
Not all fat tissue is created equal. Our bodies contain three different types of the stuff; white fat, which is primarily used for storing energy and has a low rate of metabolism (and is the main culprit for making us overweight); brown fat, which contains high levels of mitochondria and burns more readily to keep the body warm; and recently discovered beige fat, which is basically a mix of white and brown fat cells and shares some of the easy-burning properties of brown fat.
In response to exposure to cold, brown-like fat cells can develop in white fat, converting it into beige fat, which, like brown fat, burns up to help keep the body warm. This releasing of heat is called thermogenesis and a hormone called norepinephrine plays a pivotal role in the process. The effects of the hormone are achieved on the surface of the fat cells, before it is taken up into the cells where it is degraded to prevent overstimulation. However, the researchers point out the rate of norepinephrine uptake is relatively low, leading them to hypothesize there was another pathway involved.
In their study, the researchers found high levels of a protein called organic cation transporter 3 (OCT3) in the beige fat cells of mice. This protein can prompt the uptake of norepinephrine into the fat cells for degradation, and when the research team reduced the levels of OCT3 – thereby causing more norepinephrine to remain in circulation – the mice exhibited an increased rate of fat metabolism in their beige fat, along with a higher body temperature. Additionally, when mice deficient in OCT3 were exposed to prolonged cold, their beige fat content increased faster than control mice with normal levels of OCT3.
Although more work will need to be done to ascertain whether similar results would be seen in humans, by examining human genetic association databases the team did find a link between a higher metabolic rate and people with versions of the OCT3 gene that produces OCT3 protein with a reduced transport function.
"Our finding that a reduction in OCT3 activity can lead to more beige fat and increased thermogenesis indicating the importance of this transporter in catecholamine recycling in adipose tissues," says Ligong Chen of Tsinghua University in Beijing. "Developing specific OCT3 inhibitors would open up new therapeutic possibilities for metabolic diseases."
The team's research was published in PLOS Biology.
Source: Tsinghua University via Scimex
