Led by scientists at the University of Bonn, the research centers on important differences between white and brown fat and the way the body promotes one type. Among them, white fat is where the body stores excess energy in the form of a beer belly, while brown fat is responsible for burning lipids and glucose to generate body heat. This keeps us warm in cold temperatures and positions brown fat as the more desirable of the two forms.
“Nowadays, however, we are warm even in winter,” says study author Alexander Pfeifer, “so our body’s own stove is hardly needed anymore.”
In addition, a lifestyle involving a high-energy Western diet and little exercise impairs the health of brown fat cells in the body. These factors cause their function to deteriorate and the cells eventually die. Cell death in other parts of the body triggers the release of specific patterns of metabolites, so scientists began to explore this phenomenon in brown fat specifically.
“Dying cells are known to release a mix of messenger molecules that affect the function of their neighbours. We wondered if this mechanism is also present in brown fat,” explains Dr Birte Niemann, author of the paper on the study.
The team’s experiments involved subjecting brown fat cells to severe stress to trigger their death. The scientists found that these cells secrete a molecule called purine inosine in high quantities, which in turn stimulates energy expenditure in neighboring healthy brown fat cells. Mice on a high-fat diet treated with inosine remained leaner and protected from diabetes than control mice, and also experienced brown to white fat conversion.
The scientists traced these effects to a protein in the cell membrane that transports inosine into the cell, reducing the concentration outside the cell, which in turn weakens the molecule’s positive effect on energy expenditure. About 2 to 4 percent of people have genetic variants that inhibit the activity of this inosine transporter, and by studying these effects through genetic analysis of 900 subjects, scientists have uncovered some useful insights.
“Our colleagues at the University of Leipzig have carried out genetic analyses of 900 people, and those with less active transporters were, on average, significantly thinner,” says Pfeifer.
The scientists also took a drug developed to treat blood clotting disorders that happens to inhibit the inosine transporter and administered it to mice, which saw them burn more energy. This raises the prospect that drugs targeting this mechanism could be deployed as a treatment for obesity, although further research is needed to determine the safety and efficacy of this approach.
“However, further studies in humans are needed to clarify the pharmacological potential of this mechanism,” said Pfeifer. “Currently existing treatments are not yet effective. Therefore, we urgently need drugs to normalize energy balance in obese patients.”