Immune cells, including eosinophils, reside within healthy adipose tissue (AT) and the suite of immune cells is different in adipose tissue from obese individuals. Recently, it has been shown that adipose tissue-resident eosinophils (ATE) play an important role in regulating energy metabolism in adipose tissue. Eosinophil-deficient ΔdblGATA mice have increased adiposity compared to wild-type C57BL/6 mice when fed a high-fat diet (HFD), whereas hypereosinophilic IL5tg mice have smaller AT and better glucose tolerance. Although ATE typically present in small numbers in AT, the number inversely correlates with severity of obesity. While previous studies have shown that ATE number is reduced in HFD-fed mice, the transcriptional changes that occur in ATEs during obesity remain unexplored.
To investigate the response and potential role of ATE in obesity, we harvested the inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) from C57BL/6JAusb mice fed either a chow or HFD for 12 weeks. Fluorescence-activated cell sorting was used to isolate ATE from both depots for bulk RNA-sequencing. Consistent with literature, we saw a reduction in ATE number when normalized to tissue weight in the HFD mice. In iWAT, 659 genes were upregulated and 551 genes were downregulated, while in eWAT, 436 genes were upregulated and 796 genes were downregulated in ATEs from HFD-fed mice compared with chow-fed controls (adjusted p-value < 0.1). Over-representation analysis and gene set enrichment analysis identified dysregulation of numerous biological processes and pathways, including immune regulation and cytokine signalling, in ATEs from HFD-fed mice.
In this study, we show that obesity is not only associated with reduced ATE abundance but also extensive transcriptional alterations in a murine model of diet-induced obesity. These findings suggest potential functional changes in ATEs in obesity and warrant further investigation.