High fat diet attenuates the anticontractile activity of aortic PVAT via a mechanism involving AMPK and reduced adiponectin secretion

Almabrouk, T. A.M. , White, A. D., Ugusman, A. B., Skiba, D. S., Katwan, O. J., Alganga, H., Guzik, T. J., Touyz, R. M. , Salt, I. P. and Kennedy, S. (2018) High fat diet attenuates the anticontractile activity of aortic PVAT via a mechanism involving AMPK and reduced adiponectin secretion. Frontiers in Physiology, 9, 51. (doi:10.3389/fphys.2018.00051) (PMID:29479319) (PMCID:PMC5812172)

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Abstract

Background and aim: Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK. Methods: Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later. Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice. Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to HFD.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:White, Dr Anna and Salt, Dr Ian and Skiba, Mr Dominik and Guzik, Professor Tomasz and ALMABROUK, Tarek Ali Mohamed and Katwan, Omar Jassim and ALGANGA, Husam S F and Kennedy, Dr Simon and Binti Ugusman, Dr Azizah and Touyz, Professor Rhian
Authors: Almabrouk, T. A.M., White, A. D., Ugusman, A. B., Skiba, D. S., Katwan, O. J., Alganga, H., Guzik, T. J., Touyz, R. M., Salt, I. P., and Kennedy, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Frontiers in Physiology
Publisher:Frontiers Media
ISSN:1664-042X
ISSN (Online):1664-042X
Published Online:09 February 2018
Copyright Holders:Copyright © 2017 The Authors2018 Almabrouk, White, Ugusman, Skiba, Katwan, Alganga, Guzik, Touyz, Salt and Kennedy
First Published:First published in Frontiers in Physiology 9:51
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES