Obesity could be treated in other ways than using drugs suppressing appetite, a study reveals. 

Researchers identified how brown fat cells, which are linked to weight loss, communicate to expand nerve and blood vessel networks, boosting heat generation. The findings, published in Nature Communications, hint at new ways to treat obesity beyond approaches focusing on suppressing appetite. 

Most of the fat in human bodies is white fat, which stores excess energy, but leads to obesity at too high levels. Brown fat is a specialised tissue that regulates body temperature and is closely linked to weight loss and metabolic health, but humans and other mammals have smaller amounts. 

When brown fat is activated by exposure to cold, it uses the body’s resources including glucose and lipids to generate heat, a process called thermogenesis. While research on brown fat has largely focused on stimulating fat cells to generate heat, less is known about how these underlying networks function, which could help treat obesity. 

“During thermogenesis, all of that chemical energy is dissipated as heat instead of being stored in the body as white fat,” said Farnaz Shamsi, Assistant Professor of Molecular Pathobiology at NYU College of Dentistry and the study’s senior author.  

“By rapidly taking up and using fuel sources from our bodies and the food that we eat, brown fat acts like a metabolic sink that draws in nutrients and prevents them from being stored.” 

Findings ‘could be relevant in human obesity’

In the study, researchers used single-cell RNA sequencing to identify SLIT3, a protein secreted by brown fat cells, which was thought to play a role in how fat cells communicate.  

When produced, SLIT3 gets cleaved into two different fragments. Using a combination of approaches in human and mouse cells, the researchers discovered the enzyme BMP1 cleaves SLIT3 into two. They determined that the two SLIT3 fragments control different processes: one grows the network of blood vessels, while the other expands the network of nerves.  

Researchers also identified the receptor, PLXNA1, that binds to one of the SLIT3 fragments to control brown fat’s network of nerves. In studies in mice — which typically have very active brown fat and can tolerate cold temperatures for long periods of time — removing SLIT3 or the PLXNA1 receptor from brown fat resulted in mice becoming sensitive to cold and having difficulty maintaining their body temperatures. 

To see if the findings translated to humans, researchers examined samples of fat tissue from more than 1,5000 people, some of whom had obesity. Focusing on the gene that produces SLIT3, which prior studies show is associated with obesity and insulin resistance, they found that SLIT3 gene expression may regulate fat tissue health, inflammation, and insulin sensitivity in people with obesity.  

Most weight loss drugs, including GLP-1s, work to suppress appetite, decreasing the amount of food people eat and therefore the amount of energy stored. However, processes involved in brown fat could be harnessed for their therapeutic potential. 

“That really got our attention, as it suggests that this pathway could be relevant in human obesity and metabolic health,” Shamsi added. 

The post Obesity could be treated without suppressing appetite  appeared first on Drug Discovery World (DDW).