Newly Identified Molecule Can Burn Body Fat

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The researchers believe their discovery could one day be used as a treatment for obesity.

Researchers have discovered a new signaling molecule that forces brown fat cells to expend more energy.

Normally, fat cells store energy. However, in brown fat cells, energy is lost as heat, turning brown fat into a biological heater. This mechanism is therefore present in most mammals. In humans, brown fat keeps babies warm and in adults, brown fat activation correlates favorably with cardio-metabolic health.

“Today, however, we are nice and warm even in winter,” explains Prof. Dr. Alexander Pfeifer of the Institute of Pharmacology and Toxicology at the University of Bonn. “So the furnaces of our body are hardly needed anymore.”

We also move much less than our predecessors, while consuming a diet that is becoming increasingly energy-rich. Brown fat cells are poisoned by these three factors: they gradually stop working and die. On the other hand, the world population of extremely overweight people continues to increase. “Research groups all over the world are therefore looking for substances that stimulate brown fat and thus increase fat burning,” says Pfeifer.

Human brown adipocytes

Human brown adipocytes, lipid stained red (RedO oil slick). Credit: Laia Reverte Salisa / University of Bonn

Dying fat cells stimulate the energy burning of their neighbors

Together with a group of colleagues, the team from the University of Bonn has now identified a key molecule called inosine, which is able to burn fat. “It is known that dying cells release a mix of messenger molecules that affect the function of their neighbors,” explains Dr. Birte Niemann of Pfeifer’s research group. Together with her colleague Dr. Saskia Haufs-Brusberg planned and conducted the central experiments of the research. “We wanted to know whether this mechanism also occurs in brown fat.”

The researchers therefore studied brown fat cells that were under severe stress, so that the cells almost died.

“We found that they secrete the purine inosine in large amounts,” Niemann says.

What was even more intriguing, however, was the way intact brown fat cells responded to the molecular cry for help: they were activated by inosine (or simply by dying cells in their environment). So inosine fueled the furnace in them. White fat cells were also converted into their brown siblings. Mice fed a high-energy diet and inosine treatment at the same time remained thinner than control animals and were protected from developing diabetes.

Human brown adipocyte cells

Another image of human brown adipocytes, lipid stained red (RedO oil slick). Credit: Thorsten Gnad/University of Bonn

The inosine transporter seems to play an important role in this: this protein in the cell membrane brings inosine into the cell, reducing extracellular levels. As a result, inosine loses its ability to promote combustion.

The drug inhibits the inosine transporter

“There is a drug that has actually been developed for clotting disorders, but also inhibits the inosine transporter,” says Pfeifer, who is also a member of the transdisciplinary research areas of “Life and Health” and “Sustainable Futures” at the University of Bonn. “We gave this drug to mice and as a result, they burned more energy.” Humans also have an inosine transporter. It is less active in two to four percent of all people due to a genetic variation. “Our colleagues from the University of Leipzig genetically analyzed 900 individuals,” explains Pfeifer. “The subjects with the less active transporter were significantly slimmer on average.”

These results suggest that inosine also regulates thermogenesis in human brown fat cells. Substances that interfere with transporter activity may therefore be suitable for the treatment of obesity. The already approved drug for clotting disorders could serve as a starting point. “However, further studies in humans are needed to clarify the pharmacological potential of this mechanism,” says Pfeifer.

He also does not believe that a pill alone will be the solution to the rampant obesity pandemic in the world. “But the available therapies are not effective enough at the moment,” he emphasizes. “We therefore urgently need drugs to normalize energy balance in obese patients.”

Reference: “Apoptotic brown adipocytes increase energy expenditure via extracellular inosine” 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 Schlein, Azin Jafari, Holger K. Eltzschig, Thorsten Gnad, Matthias Blüher, Natalie Krahmer, Peter Kovacs, Joerg Heeren and Alexander Pfeifer, 5 July 2022, Nature.
DOI: 10.1038/s41586-022-05041-0

The study was funded by the German Research Foundation and the National Institute of Health (USA).


The Valley Voice
The Valley Voicehttp://thevalleyvoice.org
Christopher Brito is a social media producer and trending writer for The Valley Voice, with a focus on sports and stories related to race and culture.

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