Cutting down on protein can turn regular fat into a calorie burner, study finds

A new study from UCSF shows that suppressing protein turns ordinary fat into a calorie-burner, which may explain why drug trials attempting to accomplish the feat have been unsuccessful.

Researchers at the University of California, San Francisco have discovered a way to turn normal, calorie-storing white fat cells into beige fat cells, which burn calories to keep you warm.

The discovery could open the door to the development of new classes of weight-loss drugs and may explain why clinical trials of related treatments have been unsuccessful.

Until now, researchers thought that to make beige fat, you had to start with stem cells. Clinical Research Journalshowed that they could convert normal white fat cells into beige fat simply by restricting protein production.

“Many people thought this was impossible to achieve. We've shown that not only is this method effective at turning white fat cells into beige fat cells, but that the hurdles to getting there aren't as high as we thought.”

Brian Feldman, M.D., Walter L. Miller, M.D. Distinguished Professor of Pediatric Endocrinology, and senior author of the study

Fat transformation

Most mammals have three different “shades” of fat cells: white, brown, and beige. White fat acts as the body's energy store, while brown fat cells burn energy and release heat, helping to maintain body temperature.

Beige fat cells have both of these characteristics: they burn energy, and unlike brown fat cells, which grow in clumps, they are embedded throughout white fat deposits.

Humans and many other mammals are born with brown adipose tissue that helps maintain body temperature after birth, but while human babies lose their brown adipose tissue after the first year of life, their beige adipose tissue remains.

Humans can naturally transform white fat cells into beige fat cells in response to diet or a cold environment, and the scientists sought to mimic this by coaxing stem cells to transform into mature beige fat cells.

But stem cells are rare, and Feldman wanted to find a switch that could turn white fat cells directly into beige fat cells.

“For most of us, white fat cells are not uncommon, and we're happy to say goodbye to some of them,” he said.

Rats and humans

Feldman knew from previous experiments that a protein called KLF-15 plays a role in metabolism and fat cell function.

Feldman and postdoctoral researcher Liang Li, PhD, decided to investigate how this protein works in mice that retain brown fat throughout their lives. They found that the amount of KLF-15 in white fat cells was much lower than in brown or beige fat cells.

They then bred mice with white fat cells that lacked KLF-15, and the mice changed their fat cells from white to beige. Not only did the fat cells change from one form to another, but without the protein, the default setting seemed to be beige.

The researchers next investigated how KLF-15 exerts this effect: in cultured human fat cells, they found that the protein controls the amount of a receptor called Adrb1, which helps maintain energy balance.

Scientists knew that stimulating a related receptor, Adrb3, caused mice to lose weight, but human trials of drugs that act on this receptor have had disappointing results.

Feldman said another drug that targets the human Adrb1 receptor is more likely to work and could offer big advantages over the newer injectable weight-loss drugs that aim to suppress appetite and blood sugar levels.

Because Feldman's approach targets fat deposits rather than the brain, it may avoid side effects like nausea, and the effects may be long-lasting because fat cells are relatively long-lived.

“We're not there yet, but we're close enough to see clearly that these findings could have a major impact on obesity treatment,” he said.