Researchers have discovered a new type of beige fat cell that may help prevent obesity and metabolic disease by aiding in energy metabolism and generating heat through a unique internal process, suggesting potential new therapies for weight management and improving metabolic health.
There are three types of fat cells: white, brown, and beige. White fat cells store energy in the form of fat. This is essential for the body, but too many can cause health problems. Brown fat cells are especially active in infants. Brown fat cells produce heat, helping to keep an infant warm.
However, the amount of brown adipose tissue decreases throughout life, and there is very little of it left in adults. And finally, there are beige fat cells. Beige fat cells also produce heat, but not as well as brown fat cells. Beige fat cells are also present in adults and are scattered throughout the white adipose tissue, especially in the neck and shoulder area, where they help burn off excess energy.
Now, an international research team has discovered and characterized a new type of beige fat cell that is different from anything known so far. “This new beige type of fat cell plays a key role in the energy metabolism of the human body and has a positive impact on metabolic diseases and obesity,” says Anand Sharma, a postdoctoral researcher in the group of Professor Christian Wolfram at ETH and co-author of the study. “That’s why it’s so important to have a detailed understanding of how fat cells function.”
The study was led by ETH Zurich, the University of Basel, University Medical Center Leipzig and the Dana-Farber Cancer Institute in Boston. Numerous hospitals and research institutes around the world also participated in the project.
Independent of known proteins
Beige fat cells, which researchers are already familiar with, produce heat in the same way as brown fat cells: through a protein called UCP1. This protein sits inside the two membranes that surround mitochondria, the structural units known as the cell’s power plants. As part of their normal function, mitochondria pump protons into the space between the two membranes.
Protons are electrically charged subatomic particles that generally play a key role in the energy conversion process within cells. Both brown and typical beige fat cells contain the protein UCP1, which forms very narrow channels in the inner membrane through which protons can flow back into the mitochondria, generating heat through friction.
In recent years, scientists have discovered that beige fat cells that do not have the UCP1 protein also exist and that these also consume energy and generate heat. A research team from ETH Zurich and participating institutions has precisely characterized the new type of beige fat cell and shown how it does this via a “Sisyphus mechanism”.
Here’s how it works: Every biochemical process that happens in a cell always generates some heat. The new kind of beige fat cell takes advantage of this, shuttling individual processes back and forth aimlessly. It mainly involves two conversion processes: in one, the cell breaks down fat into its components (fatty acids) at full speed, then assembles them just as fast into new fat. In the other, it applies enzymes to convert creatine molecules into a related molecule, creatine phosphate, which is then quickly converted back into creatine. Scientists call these back-and-forth processes “futile cycles.” They don’t add anything to your overall biochemical budget, but they do consume energy and generate heat.
Preventing diabetes and obesity
The team first described a new type of beige fat cell in mice. They then looked at human adipose tissue and were able to demonstrate that these fat cells are also present there. While less than half of the population has the classical beige fat cell type previously known, almost all humans have the new non-circulating type, although in varying amounts.
As the researchers showed, people with a higher number of beige fat cells – both the traditional and this new type – tend to be leaner and have better metabolic health and are therefore less susceptible to metabolic disorders such as obesity and diabetes. “Beige fat cells convert energy into heat, which helps to break down excess fat,” explains ETH doctoral student Tongtong Wang from ETH Professor Wolfram’s group and first author of the study.
The researchers also explain how their new findings could be applied medically in the future. For example, it may be possible to transplant beige fat cells into people who have few of them and suffer from metabolic or weight problems. They could also develop drugs to activate beige fat cells, which are often inactive. Such drugs could be used to treat people with high blood sugar levels or former overweight people who have lost weight through surgery or other means. “Activating beige fat cells could help maintain lower body weight in the long term,” Sharma says.
Reference: “Single-nucleus transcriptomics identifies distinct classes of UCP1 and futile cycling adipocytes,” Tongtong Wang, Anand Kumar Sharma, Chunyan Wu, Claudia Irene Maushart, Adhideb Ghosh, Wu Yang, Patrik Stefanicka, Zuzana Kovanicova, Jozef Ukropec, Jing Zhang, Myrtha Arnold, Manuel Klug, Katrien De Bock, Ulrich Schneider, Cristina Popescu, Bo Zheng, Lianggong Ding, Fen Long, Revati Sumukh Dewal, Caroline Moser, Christian Wolfrum, July 30, 2024; Cell metabolism.
DOI: 10.1016/j.cmet.2024.07.005
