Solving the puzzle of converting fat-storing cells into fat-burning cells

Written By Mark

Researchers have discovered how to turn normal white fat cells, which store calories, into beige fat cells that burn calories to maintain body temperature. The discovery could open the door to a new class of weight-loss drugs.

The study was conducted by researchers from the University of California, San Francisco, USA, and its results were published in the journal Clinical Investigation on July 1, and were written about by the EurekAlert website.

Types of fat cells

Many mammals have three types of fat cells: white, brown, and beige. White fat acts as an energy store in the body, while brown fat cells burn energy to release heat, which helps maintain body temperature.

Beige fat cells combine the characteristics of the previous two types. They burn energy as brown cells do, but they are embedded throughout the white fat deposits, unlike brown fat cells that grow in clumps.

Humans and many other mammals are born with brown fat deposits that help them maintain body temperature after birth. These cells disappear from a human baby’s body during the first year of life, while beige cells remain.

Humans can naturally convert white fat cells into beige fat cells in response to diet or a cold environment. Scientists have tried to mimic this by converting stem cells—cells that can develop into different types of cells—into mature beige fat cells, but stem cells are rare.

Brian Feldman, a professor of pediatric endocrinology and the study’s lead author, wanted to find a switch that would allow him to convert white fat cells directly into beige ones. “For most of us, white fat cells are not rare, and we would be happy to give up some of them,” he says.

Mice and humans

Feldman knew from previous experiments that a protein called KLF-15 plays a role in metabolism and fat cell function, and he decided to investigate how the protein worked in mice that retained brown fat throughout their lives. He and his team found that KLF-15 was less abundant in white fat cells than in brown or beige fat cells.

When they then bred mice with white fat cells that lacked KLF15, the mice’s cells turned from white to beige, and it appeared that the cells without the protein were originally beige.

The researchers then looked at how KLF15 exerts this effect, growing human fat cells and finding that the protein controls the abundance of a receptor called ADRP1, which helps maintain energy balance.

Scientists have learned that stimulating a related receptor called AdRP3 causes mice to lose weight, but the results of experiments using drugs that act on this receptor have been disappointing. According to Feldman, a different drug that targets AdRP1 is likely to work in humans. “We’re certainly not at the finish line, but we’re close enough that you can see how these discoveries could have a big impact on treating obesity,” he says.