Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2023

Adipose eosinophils promote angiogenesis via Vascular Endothelial Growth Factor A (VEGFA) (98184)

Annalise M Psaila 1 , Manan Shah 1 , Alexander J Knights 1 , Emily J Vohralik 1 , Nadia Iannarella 2 , Rhys Allan 2 , Kate G R Quinlan 1
  1. School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW, Australia
  2. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

The rapid expansion of adipose tissue seen with obesity creates a dysregulated microenvironment characterized by impaired angiogenesis, fibrosis, and chronic inflammation. Adipose resident immune cells, including eosinophils, are important for maintaining the metabolic homeostasis of adipose tissue (Vohralik, Psaila, Knights and Quinlan, Clin Exp Pharmacol Physiol, 2020). We seek to understand and exploit the beneficial effects of adipose eosinophils to promote metabolic health in people with obesity.

Bulk RNA-seq was performed on primary murine eosinophils isolated from the blood and adipose tissue by Fluorescently Activated Cell Sorting (FACS) (Shah, Knights, Vohralik, Psaila and Quinlan, J Leuko Biol, 2023). Gene set enrichment analyses revealed that adipose eosinophils significantly upregulate genes involved in the process of angiogenesis compared to blood eosinophils. We identified Vascular Endothelial Growth Factor A (Vegfa), a key signaling molecule for the promotion of new blood vessels, as the most highly expressed angiogenic gene in adipose eosinophils (Log2FC = 6.66, padj = 3.25E-44).

To explore the role of adipose eosinophils further, we utilized a transgenic mouse model that contains supraphysiological levels of eosinophils (IL-5-tg mice), including within the adipose tissue. We found that the subcutaneous adipose tissue of IL-5-tg mice had significantly increased expression of Vegfa (p = 0.0286), with a substantial elevation in VEGFA protein as measured by western blot. Adipose tissue depots of IL-5-tg mice displayed a significant elevation in CD31+ endothelial cells compared to wild type control mice (p = 0.0286) as measured by flow cytometry, which was further validated by a significant elevation in the expression of numerous endothelial cell marker genes by qPCR.

We have identified a novel role for eosinophils in the promotion of angiogenesis within the adipose tissue, providing a new therapeutic target for potential manipulation in people with obesity.

  1. Vohralik, E.J., Psaila, A.M., Knights, A.J., and Quinlan, K.G.R. (2020) EoTHINophils: Eosinophils as key players in adipose tissue homeostasis. Clin. Exp. Pharmacol. Physiol.
  2. Shah, M., Knights, A.J., Vohralik, E.J., Psaila, A.M., and Quinlan, K.G.R. (2023) Blood and adipose-resident eosinophils are defined by distinct transcriptional profiles. J. Leuko. Biol.