Brown fat: How cells generate heat and burn fat in the process

Brown adipocytes, special fat cells, help to maintain body temperature and convert calorie-rich nutrients into heat. This protects against obesity and metabolic diseases. An international team of researchers led by Professor Alexander Bartelt from the Institute for Prophylaxis and Epidemiology of Cardiovascular Diseases (IPEK) has now deciphered a new mechanism for increasing the cellular respiration of brown fat cells. The researchers hope that this discovery will lead to new approaches for using brown fat to combat metabolic diseases. The results were recently published in The EMBO Journal .

Brown adipocytes attack fat deposits

The activation of fat-burning cells melts away the pounds. When it gets cold, the brown adipocytes get their fuel from stored fat, because thermogenesis costs a lot of calories. “People who train their brown fat through regular exposure to cold are thinner and have less diabetes and cardiovascular disease,” says Bartelt. Brown fat cells are particularly rich in mitochondria, the power stations in which cellular respiration takes place. However, how brown fat cells produce heat and boost the metabolism is not yet sufficiently understood to develop new therapies.

Cold stimulates thermogenesis

An important trick of brown fat cells is the uncoupling protein-1, which ensures that heat is produced instead of ATP, the conventional product of cellular respiration. “The high metabolic activity of brown fat cells must also influence the production of ATP,” says Bartelt, ”and we assumed that this process would be regulated by cold.” Together with Brazilian colleagues from São Paulo, the researchers identified the “inhibitory factor-1”, which ensures that ATP production is maintained instead of thermogenesis. When it gets colder, the level of inhibitory factor-1 drops and thermogenesis can take place. If the inhibitory factor-1 level is artificially increased, adaptation to cold is disturbed.

These findings were obtained in isolated mitochondria, cultured cells and in animal models. “Even though we have found an important piece of the puzzle for understanding thermogenesis, there is still a long way to go before it can be used therapeutically,” explains Dr. Henver Brunetta, who played a key role in the study. According to the authors, most people make too little use of their brown fat and it is atrophied. The new study results indicate that there are molecular switches that make the mitochondria of brown fat cells work better. This is where Bartelt and his colleagues want to start in the future. “Ideally, based on our data, we will find new ways to make the mitochondria in white fat cells fit again, because most people have enough of them,” hopes Bartelt.

Henver S. Brunetta et al.: IF1 is a cold-regulated switch of ATP synthase to support thermogenesis in brown fat. The EMBO Journal 2024