title: The Role of O-GlcNAcylation in Perivascular Adipose Tissue Dysfunction of Offspring of High-Fat Diet-Fed Rats.
abstract: Perivascular adipose tissue (PVAT), which reduces vascular contractility, is dysfunctional in the male offspring of rats fed a high-fat diet (HFD), partially due to a reduced NO bioavailability. O-GlcNAcylation of eNOS decreases its activity, thus we investigated the role of O-GlcNAcylation in the prenatal programming of PVAT dysfunction. Female Sprague-Dawley rats were fed either a control (10% fat) or an obesogenic HFD (45% fat) diet for 12 weeks prior to mating, and throughout pregnancy and lactation. Offspring were weaned onto the control diet and were killed at 12 and 24 weeks of age. Mesenteric arteries from the 12-week-old offspring of HFD dams (HFDO) contracted less to U46619; these effects were mimicked by glucosamine in control arteries. PVAT from 12- and 24-week-old controls, but not from HFDO, exerted an anticontractile effect. Glucosamine attenuated the anticontractile effect of PVAT in the vessels from controls but not from HFDO. AMP-activated protein kinase (AMPK) activation (with A769662) partially restored an anticontractile effect in glucosamine-treated controls and HFDO PVAT. Glucosamine decreased AMPK activity and expression in HFDO PVAT, although phosphorylated eNOS expression was only reduced in that from males. The loss of anticontractile effect of HFDO PVAT is likely to result from increased O-GlcNAcylation, which decreased AMPK activity and, in males, decreased NO bioavailability.
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
authors.forename: Karolina E
authors.initials: KE
authors.lastname: Zaborska
authors.forename: Gillian
authors.initials: G
authors.lastname: Edwards
authors.forename: Clare
authors.initials: C
authors.lastname: Austin
authors.forename: Mark
authors.initials: M
authors.lastname: Wareing
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006031:Glycosylation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011499:Protein Processing, Post-Translational; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; O-GlcNAcylation; Perivascular adipose tissue; Prenatal programming