Immune signaling molecule boosts fat-burning to prevent obesity
There are different types of fat in the body that perform very different roles, and by promoting the production of one over the other scientists hope to develop new forms of treatment for conditions like obesity and diabetes. Scientists in China have identified a new mechanism by which the immune system boosts the production of fat in one of its favorable forms, with experiments demonstrating how it can be leveraged to prevent obesity and diabetes in susceptible mice.
Brown fat is the type that gives babies their chubby cheeks and is activated by the body in response to cold temperatures, and subsequently burned away to keep us warm. White fat, on the other hand, is the stubborn, undesirable type that builds up when we consume excess calories and don't burn them away through physical activity, resulting in beer bellies and love handles.
Scientists have recently discovered another type called beige fat, which is genetically distinct from white and brown but like brown fat, possesses high amounts of mitochondria and shares its capacity of more easily burning away calories. Unlike brown fat, which is gradually lost as we age, however, humans maintain the ability to produce beige fat throughout adulthood in response to cold and certain hormones, which has made it a popular target amongst anti-obesity researchers.
Much of this centers on ways we might be able to convert undesirable white fat into healthier brown or beige fat, but one promising avenue relates to the way the immune system communicates with fat cells and influences the shape that they take. One interesting example of this emerged last year through a study showing how a type of immune cell known as eosinophils could be implanted into healthy mice to boost activation of beige fat, and protect them against obesity.
There are parallels to be drawn between that research and this new study from scientists at China's Sun Yat-Sen University, whose work focuses on cytokines, which are immune system signaling molecules that the team had previously found play a role in regulating beige fat production. The scientists sought to dig further into this, and explore ways the molecule might be manipulated for the purposes of heightened fat burning.
The scientists' latest round of experiments focused on a type of cytokine called interleukin-25 (IL-25) and its role in mice, with the team showing how boosting levels of the molecule, which is also found in humans, resulted in a greater production of beige fat, mimicking the effects of cold temperatures and hormonal stimulation.
Further investigations revealed a signaling chain behind this phenomenon, which started with IL-25 interacting with two other cytokines to regulate immune cells called macrophages, which in turn boosted production of a neurotransmitter within beige fat tissue to promote its generation. Ultimately, administering IL-25 to mice on a high-fat diet proved to protect them from becoming obese, and also improved their ability to maintain an insulin response, something that is hampered in those suffering from chronic obesity.
“Our results show that interleukin-25 plays a key role in production of beige fat,” says Zhonghan Yang, who led the study. “And point toward increasing interleukin-25 signaling as a potential treatment for obesity.”
The research was published in the journal PLOS Biology.