It is known as the good “heating fat tissue”: In the so-called brown body fat, it is burned instead of stored. A study has now revealed that this function might possibly be fired up even further: Researchers have identified an endogenous substance that stimulates combustion in brown fat cells in mice. Further study results suggest that the mechanism also exists in humans and that it might be influenced by medication. The scientists say that there is literally significant potential in the discovery.
Fat is not just fat: the unpopular curves of the human body are made up of white fat cells that store excess energy. However, as research has shown in recent years, animals and humans also have a small number of fat cells that differ significantly from these energy depots. They have a rather brownish coloration, which can be traced back to a particularly large number of “cell power plants” – mitochondria. They are responsible for the heating function of these special fat cells: when it is cold, they generate heat to protect the body from hypothermia. So instead of storing energy, brown body fat uses it up. As a result, they have become the focus of researchers who deal with metabolic problems such as obesity and diabetes – including the team led by Alexander Pfeifer from the University of Bonn.
The “good” body fat in sight
“Working groups around the world are looking for active ingredients that stimulate brown fat and thus increase fat burning,” says Pfeifer. Because, as he explains, the natural potential of this tissue is severely compromised by the modern way of life. “Nowadays we are pleasantly warm even in winter. Our body’s own incinerators are therefore hardly ever used and at the same time many people are eating more and more energy and moving little. These three factors are poison for the brown fat cells,” explains the researcher. They gradually cease to function and eventually even die. This in turn can further increase the problem of obesity with all its consequences.
In order to search for factors that favorably influence brown fat cells, the scientists chose a research approach that initially seems paradoxical: they exposed them to deadly stress. However, as they explain, it is known that cells that are dying often release a special mix of messenger substances, some of which may have interesting functions. “We wanted to know whether this is the same for brown fat,” says lead author Birte Niemann from the University of Bonn. The researchers examined brown fat cells from mice that they had treated in such a way that they were dying. Using metabolomics methods, they analyzed which substances – metabolites – the cells produced.
“We found that the brown fat cells released a molecule called inosine more,” says Niemann. Of particular interest, however, were the reactions to this substance that the scientists found in intact brown fat cells: they were activated by the inosine and also by dying cells in their vicinity. The signal substance kindled the incinerator in them, so to speak, and development processes also took place: white fat cells transformed into the brown versions. These results in cell cultures were then confirmed by further experiments: Mice that were fed very high-energy food and were injected with inosine remained leaner than comparison animals and were protected from diabetes, the researchers report.
Possible approaches are emerging
Through further investigations, they were then able to show that an inosine transporter plays an important role in the system. It is a special protein substance that leads to a reduction in the concentration of inosine. Due to the activity of the transporter, the signaling molecule can apparently no longer develop its combustion-promoting effect, the scientists explain. This in turn led to another discovery: “There is a drug that was actually developed to treat coagulation disorders, but also inhibits the inosine transporter,” says Pfeifer. That’s why the researchers gave it to their mice – and lo and behold: “The animals then used up more energy”.
Humans also have an inosine transporter and experiments on human cell cultures have already suggested that the functional principle with regard to the effects on brown fat is the same in mice and humans. In addition, the researchers report another “hot lead”: In two to four percent of all people, the inosine transporter is less active due to a genetic modification. “Our colleagues at the University of Leipzig genetically analyzed 900 people. Those with the less active transporter were significantly slimmer on average,” reports Pfeifer.
The results therefore indicate that inosine also regulates the burning of brown fat cells in us. There is therefore potential for substances that interfere with the activity of the transporter: they might be suitable for the accompanying treatment of obesity. The already approved active substance once morest coagulation disorders might be a suitable starting point. “We absolutely need drugs to normalize the energy balance in obese patients,” says Pfeifer. A pill alone will probably not solve the problem of obesity, which is widespread worldwide. The inosine system also needs to be researched in more detail: “Further studies in humans are needed to clarify the pharmacological potential of this mechanism,” says Pfeifer.
Source: Rheinische Friedrich-Wilhelms-Universität Bonn, specialist article: Nature: 10.1038/s41586-022-05041-0
