New research at Washington University School of Medicine has identified a way to convert white fat into brown fat. The findings, published today in Cell Reports, could help find more effective treatments for obesity and diabetes related to weight gain.
White fat stores calories and pads our bellies, hips, and thighs. In contrast, brown fat, found near our necks and shoulders, burns calories through a process that generates heat.
The researchers found that blocking the activity of the protein PexRAP in white fat triggered the fat to begin to brown into beige fat, a type of fat in between white and brown. Blocking PexRAP to create beige fat caused the fat cells to heat up and burn calories.
Although beige fat is almost like an intermediary between white fat and brown fat, it functions more like brown fat and can protect against obesity, says first author Irfan J. Lodhi, Ph.D., an assistant professor of medicine in the division of endocrinology, metabolism and lipid research at Washington University.
Lodhi’s team conducted a series of experiments in mice, creating a genetic strain of animals that didn't make PexRAP in their white fat cells. Those mice had more beige fat and were leaner than their littermates, even when they ate the same amount of food as other mice. They also burned more calories.
"Mice normally have very low levels of the protein, called PexRAP, in their brown fat," he said. "When we put the mice into a cold environment, levels of the protein also decreased in white fat, allowing that fat to behave more like brown fat. Cold induces brown and beige fats to burn stored energy and produce heat."
When Lodhi's team blocked PexRAP in the animals, the mice converted white fat into beige fat that could burn calories.
Lodhi said if the PexRAP protein could be blocked safely in white fat cells in humans, people might have an easier time losing weight.
"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," he said.
Image: Working in mice, researchers have identified a way to convert white fat, which stores calories, into brown fat that burns them. Above are white fat cells from a normal mouse (left) and from a mouse lacking the PexRAP protein (right), which interferes with the conversion of calorie-storing fat cells into calorie-burning cells. The fat cells without PexRAP store fewer calories and look more like brown fat cells. Image courtesy of Irfan J. Lodhi