Adipose tissue eosinophils play homeostatic roles and, along with other adipose tissue immune cells, regulate the activation of beige adipocytes. Beige adipocytes residing within white adipose tissue perform thermogenesis, and therefore may be able to be harnessed to reduce obesity by burning rather than storing excess fuels. We recently uncovered gene regulatory mechanisms in mice that allow adipose tissue eosinophils to secrete molecules important for beige fat activation and prevention of weight gain. Given the potential of adipose tissue eosinophils to drive beige fat activation and weight loss, we sought to generate a better understanding of these cells.
We performed bulk RNA-sequencing (RNA-seq) in mouse FACS-isolated adipose tissue eosinophils and compared gene expression to circulating blood eosinophils. We used gene set enrichment analysis to uncover pathways that were significantly enriched and upregulated in adipose eosinophils compared to blood eosinophils. Finally, we performed an analysis of the transcription factors that may drive the unique gene expression program seen in adipose eosinophils.
We found a unique transcriptional landscape in adipose tissue eosinophils that is distinct from blood eosinophils in circulation and also distinct from previously published transcriptomes of lung, colon and bone marrow eosinophils. Differential gene expression of surface receptors, chemokines and associated genes suggests that adipose tissue eosinophils adapt to their tissue niche to perform tissue-specific functions. Our analysis of transcription factors that may drive this adaptation identified the importance of KLF family, Fos/Jun families and CEBP families in regulating the transcriptome of adipose tissue eosinophils.
These findings increase our understanding of tissue-specific eosinophil heterogeneity, with implications for targeting eosinophil function to treat metabolic disorders such as obesity. We are now testing whether novel adipose tissue eosinophil secreted proteins, that we identified in our RNA-seq data, can induce beiging and increase energy expenditure and may present novel targets for obesity.