Newly Identified Molecule Can Burn Body Fat

The scientists are hopeful that one day their discovery will be utilized to treat obesity.

A new signaling molecule that compels brown fat cells to burn more energy has been found by researchers.

Fat cells often hold energy. Brown fat is a biological heater because energy is wasted as heat in brown fat cells. As a result, most mammals have this system. Human babies are kept warm by brown fat, and brown fat activation is positively correlated with cardio-metabolic health in adults.

But today, Prof. Dr. Alexander Pfeifer from the University of Bonn's Institute of Pharmacology and Toxicology says, "We're toasty warm even in cold." Therefore, the body's own furnaces are not as frequently required.

We consume a food that is growing increasingly energy-dense while also moving much less than our forebears did. These three things harm brown fat cells: They gradually stop working altogether and disappear. On the other side, the number of people who are excessively overweight is growing globally. Therefore, Pfeifer says, "Research teams all over the world are seeking for compounds that promote brown fat and thereby improve fat burning."

Red-lipid stained brown adipocytes from humans (RedO oil stain). Credit: University of Bonn/Laia Reverte Salisa

Fat cells that are aging increase their neighbors' ability to burn energy.

The team at the University of Bonn has now discovered a crucial chemical called inosine that is capable of burning fat in conjunction with a group of colleagues. According to Dr. Birte Niemann of Pfeifer's study team, "it is known that dying cells emit a mixture of messenger molecules that affect the function of their neighbors." She organized and carried out the study's key experiments with the assistance of her colleague Dr. Saskia Haufs-Brusberg. "We were curious as to whether brown fat was likewise subject to this process."

Therefore, the researchers looked at brown fat cells that had been under extreme stress to the point where the cells were almost dead.

According to Niemann, "We observed that they secrete huge amounts of purine inosine."

What was more remarkable, however, was the molecular cry for help's effect on undamaged brown fat cells, which were triggered by inosine (or simply by dying cells in their vicinity). Inosine fueled their internal fire in this way. Additionally, white fat cells had a brown sibling conversion. Mice who received both an inosine treatment and a high-energy meal at the same time remained leaner than control animals and were shielded from getting diabetes.

The inosine transporter, a protein in the cell membrane, appears to play a significant role in this situation by transferring inosine into the cell and lowering extracellular levels. Inosine consequently loses its capacity to facilitate combustion.

The medicine prevents inosine transporter activity.

According to Pfeifer, who is also a member of the University of Bonn's Transdisciplinary Research Areas "Life and Health" and "Sustainable Futures," there is a medication that was created for coagulation issues but also inhibits the inosine transporter. "The mice we given this medication to burned more calories as a result," Inosine transporters are also present in humans. It is less active in two to four percent of persons due to a genetic difference. Pfeifer states that "900 individuals have undergone genetic analysis by our colleagues at the University of Leipzig." On average, the participants with the less active transporter were noticeably thinner.

These findings imply that inosine controls thermogenesis in human brown fat cells as well. Therefore, drugs that prevent the transporter from functioning properly may be useful for treating obesity. A good place to start would be the medication that has already been approved for coagulation problems. The pharmacological potential of this pathway, however, needs to be clarified by additional research in humans, according to Pfeifer.

He also does not think that a medication will be sufficient to end the global epidemic of obesity. But, he emphasizes, "the treatments that are currently accessible are not sufficient enough." Therefore, medicine is absolutely necessary to restore the energy balance of obese people.

The study, "Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine," was published in Nature on July 5, 2022. It was conducted by Birte Niemann, Saskia Haufs-Brusberg, Laura Puetz, Martin Feickert, Michelle Y. Jaeckstein, Anne Hoffmann, Jelena Zurkovic, Markus Heine, Eva-Maria Trautmann, Christa E. Müller, Anke Tönjes, Christian                                                                 

The German Research Foundation and the National Institute of Health provided funding for the study (USA).                                                                                                                                                                                                    By UNIVERSITY OF BONN