Obesity is a global health crisis affecting more than 650 million adults worldwide. From an energy balance point of view, obesity is caused by energy imbalance, with greater energy intake than expenditure. The excess dietary energy is stored mainly as fat in adipose tissue (AT), and excessive fat storage results in obesity.
Recently, it has been shown that adipose tissue-resident eosinophils (ATE) play an important role in regulating energy metabolism in adipose tissue. ΔdblGATA mice lacking eosinophils have increased adiposity compared to wild-type C57BL/6 mice when put on a high fat diet (HFD). On the other hand, the 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. HFD-fed mice are shown to have less ATE, but the changes in gene expression in ATE are unexplored.
To study ATE’s response in and contribution to obesity, we performed bulk RNA-sequencing on FACS-sorted ATE from mice fed with chow and HFD for 10 weeks. Differential expression analysis identified 959 genes being downregulated (adjusted p-value ≤ 0.1, fold change ≤ -2) and 337 genes being upregulated (adjusted p-value ≤ 0.1, fold change ≥ 2) in ATE of HFD-fed mice. Gene set enrichment analysis identified numerous pathways, including signalling pathways of members of interleukin family and pathways related to inflammatory responses, being dysregulated in ATE from HFD-fed mice.
To further explore the heterogeneity of ATE and identify the eosinophil subtypes that contribute to AT homeostasis and pathophysiology of obesity, we are now performing single-cell RNA-sequencing on ATE in mice fed with chow and HFD. This will lay the groundwork for future development of alternative obesity treatment targeting the pathways through which eosinophils regulate energy metabolism.