Single cell RNA-sequencing suggests a novel lipid associated mast cell population following weight cycling.

Our recent study showed weight cycled mice have increased adipose mast cells compared to obese mice by single cell RNA-sequencing. Here, we aimed to confirm and elucidate these changes. Further analysis of our dataset showed that our initial mast cell cluster could subcluster into two unique populations: one with very high expression of classical mast cell markers and another with elevated lipid handling and antigen presentation genes. This new mast cell cluster accounted for most of the mast cells in the weight cycled group although it was not possible to detect the different populations by new studies with flow cytometry or Toluidine blue staining in mice, possibly due to a downregulation in classical mast cell genes. Interestingly, a pilot study in humans did suggest the existence of two mast cell populations in subcutaneous adipose tissue from obese women that appear similar to the murine populations detected by sequencing; one of which was significantly correlated with weight variance. Together, these data suggest that weight cycling may induce a unique population of mast cells similar to lipid associated macrophages. Future studies will focus on isolation of these cells to better determine their lineage, differentiation, and functional roles.