Groundbreaking research shows how white fat cells can be converted into energy-burning beige fat cells, potentially leading to new approaches for weight loss.
Scientists at UC San Francisco have found a way to change regular white fat cells, which store energy, into beige fat cells that burn calories to regulate body temperature.
This breakthrough could pave the way for the development of innovative weight-loss medications and shed light on why prior efforts in this area have not yielded successful outcomes.
In the past, it was believed that generating beige fat required starting from stem cells. However, a recent study published in the Journal of Clinical Investigation on July 1 revealed that ordinary white fat cells could be transformed into beige fat by reducing the production of a specific protein.
Lead researcher, Brian Feldman, MD, PhD, noted, “Many believed this to be impractical, but our study demonstrates that converting white fat cells to beige is achievable with a relatively low barrier.”
A Significant Change in Fat Cells
In the world of mammals, there are three types of fat cells: white, brown, and beige. While white fat functions as an energy reserve, brown fat cells burn energy to generate heat for maintaining body temperature.
Beige fat cells are a blend of these properties. They burn energy like brown fat but are distributed sporadically within white fat deposits.
Although human infants possess brown fat cells at birth to regulate body temperature, these cells diminish during the first year of life, whereas beige fat remains present.
It is possible for humans to naturally convert white fat cells into beige fat cells in response to specific diets or cold environments. Attempts have been made by scientists to induce this transformation by prompting stem cells to mature into beige fat cells.
However, since stem cells are scarce, Feldman sought a mechanism to directly shift white fat cells to beige fat cells.
Insights from Mouse and Human Studies
Previous experiments by Feldman highlighted a protein called KLF-15 that influences metabolism and fat cell function.
Collaborating with postdoctoral scholar Liang Li, PhD, Feldman explored the role of this protein in mice, which retain brown fat throughout their lives. They discovered that KLF-15 was less prevalent in white fat cells compared to brown or beige fat cells.
By breeding mice without KLF-15 in their white fat cells, the researchers observed a conversion from white to beige fat cells. Remarkably, the absence of the protein seemed to default the fat cells to beige state.
The team then investigated the mechanism through which KLF-15 exerts its influence. By studying human fat cells, they found that this protein regulates the expression of a receptor known as Adrb1, crucial for maintaining energy balance.
Although stimulating a related receptor, Adrb3, in mice led to weight loss, human trials of drugs targeting this receptor have been largely ineffective. Feldman believes that a drug aimed at the Adrb1 receptor in humans might be more successful and pose fewer side effects than existing weight-loss medications.
If successful, Feldman’s method could offer a long-lasting solution to obesity by targeting fat cells directly without impacting the brain, potentially avoiding side effects like nausea.
As Feldman remarked, “While we are not at the end of our journey, we are commensurately close to envisioning the potential impact of these findings on combating obesity.”
Liang Li was also a co-author of this study, which received funding from the NIH grant R01DK132404.
