Obesity is a severe health issue that affects many worldwide. Understanding the underlying mechanism of this condition might be the key to unlocking a potential solution or better treatments. Recent research has focused on the role of brown fat, specifically how its activation could lead to weight loss.
Headed by Professor Dr. Alexander Pfeifer, a research team at the University of Bonn has now identified a key molecule named inosine that is capable of burning fat. The result of the study is now published in the journal Nature (Niemann et al., 2022).
The findings show that inosine is a metabolite that is released from dying brown fat and has a “replace me” signaling role that controls thermogenic fat and fights obesity.
What Is Brown Fat & What Does It Do?
Brown fat is a type of adipose tissue found in humans and some other mammals. It is capable of generating significant amounts of heat to help regulate body temperature in a process called “thermogenesis”. This process of burning energy is why many researchers believe brown fat could play an important role in weight loss.
Dying Fat Cells Enhance Energy Combustion
Dr. Birte Niemann from Pfeifer’s research group says, “It is known that dying cells send out a mix of molecules that affect how their neighbors work.” She and her colleague, Dr. Saskia Haufs-Brusberg, planned and carried out the study’s main experiments. “We wanted to know if this mechanism is also in brown fat.”
So, the researchers looked at brown fat cells that were under so much stress that they were almost dead. “We found that they give off a lot of the purine inosine,” Niemann says. More interesting, though, was how intact brown fat cells responded to the molecular call for help: inosine turned them on (or simply by dying cells in their vicinity). So, Inosine turned up the heat inside them. Fat cells that were white also changed into their brown siblings. Mice that ate a high-energy diet and were given inosine at the same time stayed slimmer than control mice and didn’t get diabetes.
Inosine Transporter Inhibitor Boots Energy Combustion
Inosine gets into the cell through a protein called ‘inosine transporter’ in the cell membrane. This lowers the concentration of inosine outside the cell. So, inosine can no longer have combustion-promoting properties.
Dr. Pfeifer says, “There is a drug that was made for coagulation disorders, but it also blocks the inosine transporter.” “When we gave this drug to mice, they burned more calories.” People also have a transporter for inosine. Because of a genetic difference, it is less active in 2% to 4% of people. Pfeifer says, “Our colleagues at the University of Leipzig have looked at the genes of 900 people.” “On average, the people who had the less active transporter were much thinner.”
Based on these findings, it seems that inosine also controls thermogenesis in brown fat cells in humans. Because of this, substances that stop the transporter from doing its job could possibly be used to treat obesity. The drug that is already allowed to treat problems with blood clotting could be used as a starting point.
“However, more research on humans is needed to figure out how this mechanism could be used in medicine,” says Pfeifer. He also doesn’t think that a pill alone will stop the growing number of obese people around the world.
“But the treatments we have right now are not good enough,” he stresses.
“Therefore, we need medications as soon as possible to get the energy balance of obese patients back to normal.”