Studies identify molecules that support fat burning

A study led by the University of Bonn identified a molecule (purin inosine) that promotes fat burning in brown adipocytes. This mechanism was discovered in mice, but probably also exists in humans. If the inosin transporter activity is low, the mice remain fairly lean despite a high-fat diet. The study, which also included researchers from the University of Leipzig and the University Medical Center Hamburg-Eppendorf, is now published in the journal Nature.

Fat cells usually store energy. However, in brown fat cells, energy is dissipated as heat. Therefore, brown fat acts as a biological heater. Therefore, most mammals have this mechanism. In humans, it keeps newborns warm, in human adults, brown fat activation has a positive correlation with the health of cardiac metabolism.

But now it’s hot even in winter. So we don’t really need a kamado for our body anymore. “

Dr. Alexander Pfeifer, Institute of Pharmacology and Toxicology, University of Bonn

At the same time, we are eating an increasingly energy-dense diet, moving far less than our ancestors. These three factors are toxic to brown fat cells. They gradually cease to function and can even die in the end. On the other hand, the number of people who are overweight is increasing all over the world. “Therefore, research groups around the world are looking for substances that stimulate brown fat and increase fat burning,” says Pfeiffer.

Dying fat cells promote energy burning of neighbors

A team at the University of Bonn worked with a group of colleagues to identify an important molecule named inosin that can burn fat. “Dying cells are known to release a mixture of messenger molecules that affect the function of adjacent cells,” explains Dr. Birte Niemann of Pfeiffer’s research group. She, along with her colleague Dr. Saskia Haufs-Brusberg, planned and conducted a central experiment in her research. She said, “I wanted to know if this mechanism was also present in brown fat.”

Therefore, researchers have studied brown fat cells that have been exposed to severe stress, as if the cells were virtually dying. “We have found that they secrete large amounts of purininosine,” says Niemann. But more interesting was how the intact brown fat cells responded to calls for molecular help. They were activated by inosine (or simply by dying cells near them). Therefore, inosine fanned their internal furnaces. White fat cells were also converted to brown siblings. Mice fed a high-energy diet and simultaneously treated with inosin remained lean compared to control animals and were protected from diabetes.

The inosine transporter seems to play an important role in this context. This protein in the cell membrane transports inosine into the cell and reduces extracellular concentrations. Therefore, inosine can no longer exert its combustion-promoting effect.

The drug inhibits the inosine transporter

“There are drugs that were actually developed for coagulation disorders, but they also block innosin transporters,” said Pfeiffer, who is also a member of the University of Bonn’s interdisciplinary research areas “Life and Health” and “Sustainable Future.” say. “We gave this drug to mice, and as a result, they burned more energy.” Humans also have innocin transporters. 2-4% of all people are less active due to genetic variation. “A colleague at Leipzig University genetically analyzed 900 individuals,” explains Pfeiffer. “Subjects with low active transporter activity were significantly leaner on average.”

These results suggest that inosin also regulates heat generation in human brown adipocytes. Therefore, substances that interfere with transporter activity may be suitable for the treatment of obesity. Drugs that are already approved for coagulopathy may serve as a starting point. “But further research in humans is needed to clarify the pharmacological potential of this mechanism,” says Pfeiffer. He also does not believe that tablets alone will be the solution to the world’s prevailing obesity pandemic. “But the treatments available aren’t effective enough at this time,” he emphasizes. “Therefore, we really need medicines to normalize the energy balance of obese patients.”

The important role played by the body’s own heating system is also demonstrated by a major new participating research consortium. The German Research Foundation (DFG) recently approved a cross-regional collaborative research center where universities in Bonn, Hamburg and Munich conduct targeted research on brown fat. Adipose tissue.