Scientists looking for novel ways to treat type 2 diabetes have stumbled across a mechanism by which the immune system can trigger the secretion of fat cells through the skin. The mechanism may translate from animal studies into humans, but turning it into a safe obesity therapy could be challenging.
The research began by studying how an immune protein called thymic stromal lymphopoietin (TSLP) influences energy metabolism in mice. The initial hypothesis was that increasing the levels of TSLP in mice could lower the animals’ risk of developing diabetes.
“Initially, we did not think TSLP would have any effect on obesity itself," says the study’s principal investigator Taku Kambayashi. "What we wanted to find out was whether it could impact insulin resistance. We thought that the cytokine could correct Type 2 diabetes, without actually causing the mice to lose any weight.”
After a month of treatment designed to increase TSLP levels the mice showed significant improvements to blood glucose. But surprisingly, the animals also dropped huge volumes of visceral fat. Even more unexpectedly, the TSLP-treated mice were losing weight while consuming up to 30 percent more food than the control mice.
So what was going on? Kambayashi says the clue was in the unusually oily coats on the TSLP-treated mice.
“When I looked at the coats of the TSLP-treated mice, I noticed that they glistened in the light,” he says. “I always knew exactly which mice had been treated, because they were so much shinier than the others.”
Extracting oils from the animals’ fur the researchers discovered the mice were indeed "sweating fat." The fat cells in the oils were a form of what is called sebum – a waxy substance released by glands in the skin.
Sebum secretion is generally regulated by hormones. In humans excessive hormonal activity in adolescence is known to stimulate high levels of sebum secretion leading to that infamous wave of teenage acne.
As Kambayashi points out, this is the first evidence of sebum-secretion being influenced by an immune system mechanism.
“This was a completely unforeseen finding, but we’ve demonstrated that fat loss can be achieved by secreting calories from the skin in the form of energy-rich sebum,” says Kambayashi. “We believe that we are the first group to show a non-hormonal way to induce this process, highlighting an unexpected role for the body’s immune system.”
A subsequent investigation into the relationship between TSLP and sebum gland gene expression in humans suggested the mechanism may be transferable. Hypothetically, TSLP could trigger a similar process in humans.
“I don’t think we naturally control our weight by regulating sebum production, but we may be able to highjack the process and increase sebum production to cause fat loss,” adds Kambayashi. “This could lead to novel therapeutic interventions that reverse obesity and lipid disorders.”
Marlon Schneider, a German researcher who did not work on this new study, penned an accompanying commentary on the new findings in the journal Science. He says the challenges of turning this novel research finding into an obesity therapy are “formidable.”
Increasing TSLP levels in humans may work to trigger the secretion of fat-filled sebum, but a number of safety issues could be a problem. In mice, for example, increasing TSLP levels did cause broad immune cell infiltration into a number of organs. Plus, we do know increased sebum secretion plays a role in acne so it would be a significant challenge to mitigate any inflammatory skin condition related to an anti-obesity therapy that works by “sweating fat.”
Still, Kambayashi and his team are exploring this mechanism further in the hope of developing a novel kind of anti-obesity therapy in the future.
The new study was published in the journal Science.
Source: Penn Medicine
