Author ORCID Identifier

Park - https://orcid.org/0000-0001-8576-7531

Document Type

Article

Publication Date

9-29-2016

Publication Title

Vascular Medicine

Volume

21

Issue

6

First Page

489

Last Page

496

Abstract

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m2) and five metabolically normal non-obese (BMI 26±2 kg/m2) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (pWNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (pp

Comments

This is an Accepted Manuscript of an article published by Sage in [JOURNAL TITLE] on [date of publication], available online: [Article DOI]

Reuse restricted to noncommercial and no derivative uses.

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