Genetic Clue Into Brown Fat Energy Burning May Lead To Obesity Therapies
It’s well known that the body creates two different types of fat: white and brown, and they are bad and good, respectively.
White fat stores extra calories from high-fat foods like sugary donuts, packing on that extra “flab” until the body needs it to burn energy. Brown fat, in the meantime, has been known to burn fat by transforming it into heat.
In other words, while white fat packs onto your hips and stomach, brown fat works to burn it off. It seems rather contradictory; but brown fat’s unique ability to naturally burn white fat has piqued the interest of scientists hoping to develop new therapies to battle obesity and diabetes, both of which have become epidemics in the U.S. and around the world.
Now, researchers at Beth Israel Deaconess Medical Center (BIDMC) have pinpointed a new clue into how brown adipose tissue (BAT) burns energy. They found that the transcription factor IRF4 (a specific protein that binds to specific DNA sequences and controls genetic information) plays a significant role in the thermogenic — or energy-burning — process of brown fat.
“The discovery several years ago that brown fat plays an active role in metabolism suggested that if we could manipulate the number or activity of these fat cells, we could force our bodies to burn extra calories,” Dr. Evan Rosen, an investigator in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School, said in a press release. “Now that we have identified a major factor driving this process, we can look for new approaches to exploit this for therapeutic benefit.”
Brown fat is often activated by cold temperatures, as well as certain hormones and drugs, such as epinephrine. It’s able to generate heat through a group of genes that are known as the “thermogenic gene expression program,” one of which was pinpointed by the authors as a significant part of the brown fat burning process.
The authors write in the press release:
There has been intense interest in how the UCP1 gene is regulated, with most attention focused on a molecule called PGC1-alpha," explains Rosen."PGC1-alpha was discovered 15 years ago in the lab of coauthor Bruce Spiegelman, and is a transcriptional co-factor, which means that it indirectly drives the transcription of genes like UCP1 because it lacks the ability to bind to DNA itself. This suggested that there must be a bona fide transcription factor, or DNA binding protein, that was mediating the effects of PGC-1alpha, but despite years of work and several promising candidates, no clear partner for PGC-1alpha had been discovered to increase thermogenesis. It turns out that IRF4 is that partner.
As infants, our bodies are filled with brown fat: our organs are wrapped in it to keep us warm and adapt to life. But the older we get, the more brown fat disappears. Recently, researchers were able to discover that brown fat actually does remain in adults, however, packing into parts of our necks and other corners of the body. When brown fat is activated, in theory we could be able to eat more without gaining weight.
Recent studies have examined the role of brown adipose tissue in battling metabolic diseases like obesity, particularly since it does turn out that every adult human can produce activated BAT. But it might still be some time before there will be such a thing as a therapy for obesity using the natural powers of brown fat: many “questions remain regarding efficacy, safety, practicality, and durability of such treatments,” researchers of a 2013 study write.