SN Saxton
Interleukin-33 rescues perivascular adipose tissue anticontractile function in obesity
Saxton, SN; Whitley, AS; Potter, RJ; Withers, SB; Grencis, R; Heagerty, AM
Authors
AS Whitley
RJ Potter
Dr Sarah Withers S.B.Withers@salford.ac.uk
Associate Professor/Reader
R Grencis
AM Heagerty
Abstract
Perivascular adipose tissue (PVAT) depots are metabolically active and play a major vasodilator role in healthy lean individuals. In obesity, they become inflamed and eosinophil-depleted and the anticontractile function is lost with the development of diabetes and hypertension. Moreover, eosinophil-deficient ΔdblGATA-1 mice lack PVAT anticontractile function and exhibit hypertension. Here, we have investigated the effects of inducing eosinophilia on PVAT function in health and obesity. Control, obese, and ΔdblGATA-1 mice were administered intraperitoneal injections of interleukin-33 (IL-33) for 5 days. Conscious restrained blood pressure was measured, and blood was collected for glucose and plasma measurements. Wire myography was used to assess the contractility of mesenteric resistance arteries. IL-33 injections induced a hypereosinophilic phenotype. Obese animals had significant elevations in blood pressure, blood glucose, and plasma insulin, which were normalized with IL-33. Blood glucose and insulin levels were also lowered in lean treated mice. In arteries from control mice, PVAT exerted an anticontractile effect on the vessels, which was enhanced with IL-33 treatment. In obese mice, loss of PVAT anticontractile function was rescued by IL-33. Exogenous application of IL-33 to isolated arteries induced a rapidly decaying endothelium-dependent vasodilation. The therapeutic effects were not seen in IL-33-treated ΔdblGATA-1 mice, thereby confirming that the eosinophil is crucial. In conclusion, IL-33 treatment restored PVAT anticontractile function in obesity and reversed development of hypertension, hyperglycemia, and hyperinsulinemia. These data suggest that targeting eosinophil numbers in PVAT offers a novel approach to the treatment of hypertension and type 2 diabetes in obesity.
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 30, 2020 |
Online Publication Date | Oct 9, 2020 |
Publication Date | Dec 1, 2020 |
Deposit Date | Dec 11, 2020 |
Publicly Available Date | Dec 11, 2020 |
Journal | American Journal of Physiology-Heart and Circulatory Physiology |
Print ISSN | 0363-6135 |
Electronic ISSN | 1522-1539 |
Publisher | American Physiological Society |
Volume | 319 |
Issue | 6 |
Pages | H1387-H1397 |
DOI | https://doi.org/10.1152/ajpheart.00491.2020 |
Publisher URL | https://doi.org/10.1152/ajpheart.00491.2020 |
Related Public URLs | https://journals.physiology.org/journal/ajpheart |
Additional Information | Additional Information : ** From Crossref journal articles via Jisc Publications Router **Journal IDs: pissn 0363-6135; eissn 1522-1539 **History: issued 01-12-2020; published 01-12-2020 |
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