Eosinophils are mediators of adipose tissue angiogenesis

Adipose eosinophils confer protection against obesity and metabolic disease, yet the mechanism by which adipose eosinophils mediate this process is incompletely understood. Here we found that transgenic elevation of adipose eosinophil number results in increased adipose tissue levels of vascular endothelial growth factor A (VEGFA), with resulting elevation in adipose tissue vascularisation and production of thermogenic beige fat. We found that this process is directly regulated by Activator Protein 1 (AP-1) family member activating transcription factor 3 (ATF3), with eosinophil-specific deletion of ATF3 both in vitro and in vivo resulting in decreased adipose tissue VEGFA, reduced adipose tissue vascularisation, and decreased thermogenic beige fat. We thus propose a novel mechanism by which eosinophils promote metabolic homeostasis and highlight ATF3 as a key driver of adipose eosinophil tissue specialisation. Overall design: RNA-seq profiling of wild type EoL-1 cell and their knockdown derivative (ATF3)