It is known as the good “warming fat tissue”: in the so-called brown body fat, it is burned rather than stored. A study has now revealed that this function could be further enhanced: Researchers have identified an endogenous substance that stimulates burning in brown fat cells in mice. Further study results suggest that the mechanism also exists in humans and that it could be influenced by drugs. Scientists say 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 blood 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 stores. They are quite brown in color, which can be traced back to a particularly large number of “cellular powerhouses” – the mitochondria. They are responsible for the heating function of these special fat cells: in cold weather, they generate heat to protect the body from hypothermia. So instead of storing energy, brown body fat consumes it. As a result, they have become the focus of researchers dealing with metabolic problems such as obesity and diabetes, including the team led by Alexander Pfeifer of 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 fabric is severely compromised by the modern way of life. “Today we are pleasantly warm even in winter. The incinerators of our body are therefore almost never used and at the same time many people eat more and more energy and move little. These three factors are poison to brown fat cells, “explains the researcher. Gradually they cease to function and eventually die as well. This in turn can further increase the problem of obesity with all its consequences.
To look for the factors that favorably affect brown fat cells, scientists chose a research approach that initially seems paradoxical: they exposed them to deadly stress. However, as they explain, it is known that dying cells often release a special mix of messenger substances, some of which may have interesting functions. “We wanted to know if this is the same for brown fat,” says lead author Birte Niemann of the University of Bonn. The researchers looked at the brown fat cells of the mice they had treated so that they were dying. Using metabolomic 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 scientists found in intact brown fat cells: they were activated by inosine and also by dying cells in their vicinity. The signal substance ignited the incinerator inside them, so to speak, and developmental processes also took place: white blood cells transformed into brown versions. These results in cell cultures were then confirmed by further experiments: mice that were fed high-energy food and inosine injected remained leaner than the comparison animals and were protected from diabetes, the researchers report.
Possible approaches are emerging
Through further investigation, they were then able to demonstrate 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 has actually been developed to treat bleeding disorders, but it also inhibits the inosine transporter,” says Pfeifer. That’s why the researchers gave it to their mice – and behold: “The animals therefore consumed more energy.”
Humans also have an inosine transporter, and experiments on human cell cultures have already suggested that the functional principle regarding effects on brown fat is the same in mice and humans. In addition, the researchers report another “hot lead”: in 2-4% of all people, the inosine transporter is less active due to a genetic modification. “Our colleagues from the University of Leipzig genetically analyzed 900 people. Those with the least active transporter were on average significantly leaner, ”Pfeifer reports.
The results therefore indicate that inosine also regulates the burning of brown fat cells in us. The potential therefore exists for substances that interfere with transporter activity: they may be suitable for the accompanying treatment of obesity. The already approved active ingredient against coagulation disorders could be a valid starting point. “We absolutely need drugs to normalize the energy balance in obese patients,” says Pfeifer. One pill alone will probably not solve the problem of obesity, which is spread all over the world. The inosin system also needs to be studied in more detail: “Further human studies are needed to elucidate the pharmacological potential of this mechanism,” says Pfeifer.
Source: Rheinische Friedrich-Wilhelms-Universität Bonn, specialist article: Nature: 10.1038 / s41586-022-05041-0