New Class of Beige Fat Cells That Burn Energy Through ‘Futility Cycles’ Could Lead to Better Metabolic Health

Fat cells come in three colors: white, brown, and beige. White fat cells store fat in our bodies as an energy reserve. We need these cells, but having too many can lead to health problems.

Brown fat cells are particularly active in infants. They produce heat and thus maintain the baby’s body temperature. However, the amount of brown fat tissue decreases over the course of life; adults have very little of it.

Finally, there are beige fat cells. These can also produce heat, although less well than brown fat cells. Beige fat cells are also found in adults, scattered throughout white adipose tissue, especially in the neck and shoulder area, and burn excess energy.

Today, an international research team has discovered and described a new type of beige fat cell that is different from others.

“The new beige fat cells play an important role in the energy metabolism of the human body and have a positive effect on metabolic diseases and obesity,” says Anand Sharma, a postdoctoral fellow in the group of Professor Christian Wolfrum at ETH Zurich and co-author of the study. “That is why it is so important to understand their functioning in detail.”

The study, published in Cellular metabolismThe project was led by ETH Zurich, the University of Basel, the University Medical Center Leipzig and the Dana-Farber Cancer Institute in Boston. Many other hospitals and research institutes around the world participated in the project.

Independent of a known protein

The beige fat cells that researchers already knew about generate heat in the same way that brown fat cells do, thanks to a protein called UCP1. This protein is located inside two membranes that surround mitochondria, the structural units often referred to as the cell’s powerhouses.

As part of their normal functioning, mitochondria pump protons into the space between the two membranes. Protons are electrically charged elementary particles that generally play an important role in energy conversion processes in cells.

Brown fat cells and the classic beige fat cells described above contain the protein UCP1. This forms a very narrow channel in the inner membrane through which protons return to the mitochondria, thereby generating heat by friction.

In recent years, scientists have discovered that there are also beige fat cells that lack the UCP1 protein, which also consume energy and thus produce heat. The research team from ETH Zurich and participating institutions has now precisely characterized the new class of beige fat cells and shown how they achieve this, by means of a “Sisyphean mechanism.”

Here’s how it works: All biochemical processes that take place in cells always generate heat. The new class of beige fat cells takes advantage of this and allows individual processes to run wild, seemingly aimlessly.

There are basically two conversion processes. In the first case, cells break down fats into their components (fatty acids) at full speed, then assemble them just as quickly into new fats. In the other case, they use an enzyme to convert creatine molecules into creatine phosphate, a related molecule, and then immediately convert it back to creatine.

Scientists call these back-and-forth processes “futile cycles.” They add nothing to the overall biochemical balance, but they consume energy and generate heat.

Preventing diabetes and obesity

The research team first described the new type of beige fat cells in mice. They then examined human fat tissue and were able to show that these fat cells were also present there. While less than half of the population has the classic beige fat cell type known so far, almost all humans have the new futile-cycling type, albeit in varying amounts.

As the researchers showed, people who have a high number of beige fat cells – both the known type and this new type – are thinner and tend to have better metabolic health. They are therefore less prone to obesity and metabolic disorders such as diabetes.

“Because beige fat cells convert energy into heat, they help break down excess fat,” says Tongtong Wang, a doctoral student at ETH Zurich in the group of ETH Zurich Professor Wolfrum and lead author of the study.

The researchers also explain how these new findings could be used in the medical field in the future. For example, it would be possible to transplant beige fat cells into people who have few of them and who suffer from metabolic diseases or weight problems. It would also be possible to develop drugs that activate beige fat cells, which are often inactive.

These drugs could be used to treat people with high blood sugar or overweight people who have lost weight through surgery or other means. “Activating their beige fat cells could help them maintain their lower body weight in the long term,” Sharma says.