In ancient times, alchemists sought to convert one substance into another more highly prized substance, such as turning lead into gold. While we now know that much of what they were attempting is impossible, the modern-day alchemists that are the biologists at Washington University School of Medicine in St. Louis (WUSM) have recently achieved a goal that's nearly as impressive – turning white fat into beige fat. While it doesn't have the same cachet as a precious metal, beige and brown fats are increasingly being viewed as a valuable substances in their own right, as they burn calories and help overweight people get more lean.
White fat is the substance that accumulates around our guts and other body areas to make us look more lumpy than lean by storing excess calories. Beige and brown fat, on the other hand, contains more mitochondria than its white cousin, which allows it to burn calories such as sugar and other lipids to create heat. Having more darker fat, the thinking goes, helps the body become a more active calorie-burning furnace, which can help keep it lean.
Because of this unique characteristic of the brown fat, which is also known as brown adipose tissue (BAT), there has been a good amount of research conducted to find out how to increase its presence in our bodies. So far, researchers have found that fish oil, drug-doped nanoparticles, cold temperatures, and even the erectile-dysfunction drug Viagra can all play a role in boosting BAT. They've also seen a correlation between protein and brown fat, with one study finding that increasing the stable amount of a protein known as PRDM16in rats increased BAT, while another found that blocking substances known as Gq proteins had the same effect.
The new study from WUSM falls into the last category. They too found that blocking a protein increased beige fat, converting white fat in the process. The protein they focussed on is called PexRAP and the researchers had found that it existed in abundance in white fat, but not in brown. What's more, when mice were put into cold environments – a condition known to increase beige and brown fat – the levels of PexRAP in their white fat cells dropped, causing them to convert white fat into beige fat.
The conclusion they drew was that PexRAP is what keeps white fat from browning, so by blocking it, the white fat was free to turn beige, potentially delivering a one-two punch to obesity, which the researchers say is their goal.
In the study, the researchers created a genetically modified line of mice that couldn't make PexRAP. They found that the rodents had more brown fat than their non-modified littermates and that they were leaner even though they ate the same number of calories each day. The modified mice also exhibited a higher level of calorie burning.
The researchers say that now the trick will be figuring out how to block the protein safely in human beings.
"The challenge will be finding safe ways to do that without causing a person to overheat or develop a fever, but drug developers now have a good target," said Irfan J. Lodhi, an assistant professor of medicine at WUSM. Lodhi is the first author on a paper describing the findings that's been published today in the journal Cell Reports.