Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

Sarah B Withers,Daniel Sorobetea,Ruth Forman,Anthony M Heagerty,Selene Meza-Perez,Catherine B Lawrence,Kasia Sitnik,Sheena M Cruickshank,Thomas Hopwood,Marcus Svensson-Frej,Kathryn J Else,William W Agace

doi:10.1038/srep44571

Abstract

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function.

Highlights

The eosinophil as a key cell type controlling the release of these mediators via catecholamine mediated-activation of adipocyte-expressed β3 adrenoceptors
Immunohistochemical and flow cytometric analyses of enzymatically digested mesenteric adipose tissue demonstrated a significant reduction in the number of eosinophils present in high fat diet (HFD) mice compared with chow fed age-matched controls (P = 0.0113; Fig. 1d,e and data not shown), consistent with previous reports[12]
While a role of eosinophils in regulation of these events have not previously been recognized, our data identify mechanisms by which obesity-induced alterations to the eosinophil population may perturb the influence from perivascular adipose tissue (PVAT) on small arteries and the physiological consequences thereof[4,6]

Summary

Introduction

The eosinophil as a key cell type controlling the release of these mediators via catecholamine mediated-activation of adipocyte-expressed β3 adrenoceptors. Immunohistochemical and flow cytometric analyses of enzymatically digested mesenteric adipose tissue demonstrated a significant reduction in the number of eosinophils present in HFD mice compared with chow fed age-matched controls (P = 0.0113; Fig. 1d,e and data not shown), consistent with previous reports[12].

Results

Conclusion