Mice can lose weight through their skin

In looking into the immune system’s involvement in metabolic diseases such as type 2 diabetes, University of Pennsylvania researcher Taku Kambayashi stumbled onto an unexpected immune connection to skin oils called sebum. This link, found in mice, suggests a new potential approach for obesity treatments (Science 2021, DOI: 10.1126/science.abd2893).

Kambayashi is interested in how T cells might contribute to metabolic disease. To investigate this, his team fed mice a high-fat diet. After the rodents had gained weight, the researchers increased the mice’s levels of an inflammatory cytokine called thymic stromal lymphopoietin. This peptide activates T cells, so Kambayashi expected to see changes in the number of T cells and other immune effects. But what happened was surprising: the mice lost weight. Even when they stayed on the high-calorie diet, they lost fat mass.

After noticing that the shrinking mice also got shiny coats, the researchers analyzed the amount and type of skin oils. They found that the amount of sebum lipids on the cytokine-treated mice was up to four times the usual amount because the cytokine-activated T cells boost the activity of sebum-producing glands.

Kambayashi says he took a lot of convincing that this increase in sebum production explained the mice’s weight loss. Because sebum acts as a protective layer for the skin, he says, it makes sense that skin inflammation might trigger an increase in sebum production. Kambayashi next wants to understand the details of how T cells manage this process—and then see if what works for overweight mice could be helpful for overweight humans.