Common Fat Cells Converted to Calorie-Burning Beige Fat in Mice

According to recent research from UC San Francisco, it is now possible to convert common white fat cells, which store calories, into beige fat cells, which burn calories to regulate body temperature.

The finding in mice may pave the way for the creation of a novel class of medications intended to aid in weight loss and could also explain the failure of related clinical trials.

Scientists had previously thought that stem cells might be needed to create beige fat. By restricting the production of a protein, normal white fat cells can be changed into beige fat, according to a recent study published in the Journal of Clinical Investigation.

Brian Feldman, M.D., Ph.D., University of California San Francisco said, “A lot of people thought this wasn’t feasible.”

We showed not only that this approach works to turn these white fat cells into beige ones, but also that the bar to doing so isn’t as high as we’d thought.”

Walter L. Miller, M.D. Distinguished Professor, Pediatric Endocrinology, University of California San Francisco

A Fat Transformation

Three "shades" of fat cells are present in many mammals: white, brown, and beige. While brown fat cells burn energy to release heat, which helps maintain body temperature, white fat acts as the body's energy reserves.

These qualities are combined in beige fat cells. In contrast to brown fat cells, which proliferate in clusters, beige fat cells are enmeshed in white fat deposits and consume energy.

Brown fat deposits are present in the bodies of many mammals, including humans, and these deposits aid in regulating body temperature. However, beige fat remains after a baby's brown fat goes away during the first year of life.

When exposed to cold conditions or certain foods, humans have a natural tendency to convert white fat cells into beige ones. In an attempt to replicate this, researchers coaxed stem cells into developing into mature, beige fat cells.

However, Feldman wanted to discover a switch he could flip to instantly convert white fat cells into beige ones because stem cells are uncommon.

For most of us, white fat is not rare and we’re happy to part with some of it.”

Brian Feldman, University of California San Francisco

Mice and Humans

Feldman was aware that a protein known as KLF-15 is involved in fat cell function and metabolism from his previous research.

In collaboration with postdoctoral researcher Liang Li, Ph.D., Feldman chose to study the protein's activity in mice, as mice accumulate brown fat all their lives. They discovered that compared to brown or beige fat cells, KLF-15 was substantially less common in white fat cells.

The mice turned from white to beige when they bred mice with white fat cells devoid of KLF-15. The fat cells were not only able to change their shape, but they also looked beige by default in the absence of protein.

Next, the researchers examined KLF-15's mechanism of action. Using human fat cells as a model, they discovered that the protein regulates the amount of a receptor known as Adrb1, which contributes to the preservation of energy balance.

Researchers were aware that weight loss in mice was induced by activating a related receptor called Adrb3. However, the results of drug trials involving this receptor have been underwhelming.

Feldman suggests that an alternative medication that targets the human Adrb1 receptor has a higher chance of success and may offer notable benefits over the recently developed injectable weight-loss medications that aim to reduce blood sugar and suppress appetite.

Due to its limited activity on fat deposits rather than the brain, it might be able to avoid adverse effects like nausea. Furthermore, since fat cells have a lengthy lifespan, the effects would be cumulative.

We’re certainly not at the finish line, but we’re close enough that you can clearly see how these discoveries could have a big impact on treating obesity.”

Walter L. Miller, M.D. Distinguished Professor, Pediatric Endocrinology, University of California San Francisco