title: Adiponectin improves endothelial function in mesenteric arteries of rats fed a high-fat diet: role of perivascular adipose tissue.
abstract: OBJECTIVE
  Adiponectin, the most abundant peptide secreted by adipocytes, is involved in the regulation of energy metabolism and vascular physiology. Here, we have investigated the effects of exogenous administration of adiponectin on metabolism, vascular reactivity and perivascular adipose tissue (PVAT) of mesenteric arteries in Wistar rats fed a high-fat diet.
  
  
  METHODS
  The effects of adiponectin on NO-dependent and independent vasorelaxation were investigated in isolated mesenteric arteries from 12-month-old male Wistar rats (W12m) fed a high-fat diet (HFD) for 4 months and compared with those from age-matched rats given a control diet. Adiponectin ((96 μg·day-1) was administered by continuous infusion with a minipump, implanted subcutaneously, for 28 days.
  
  
  RESULTS
  Chronic adiponectin treatment reduced body weight, total cholesterol, free fatty acids, fasting glucose and area under the curve of intraperitoneal glucose tolerance test, compared with HFD rats. It also normalized NO-dependent vasorelaxation increasing endothelial NO synthase (eNOS) phosphorylation in mesenteric arteries of HFD rats. In PVAT from aged (W12m) and HFD rats there was increased expression of chemokines and pro-inflammatory adipokines, the latter being important contributors to endothelial dysfunction. Infusion of adiponectin reduced these changes.
  
  
  CONCLUSIONS
  Adiponectin normalized endothelial cell function by a mechanism that involved increased eNOS phoshorylation and decreased PVAT inflammation. Detailed characterization of the adiponectin signalling pathway in the vasculature and perivascular fat is likely to provide novel approaches to the management of atherosclerosis and metabolic disease.
  
  
  BACKGROUND
  This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|IBILI, University of Coimbra, Coimbra, Portugal.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Sena
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|IBILI, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Pereira
authors.affiliation: IBILI, University of Coimbra, Coimbra, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|IBILI, University of Coimbra, Coimbra, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Letra
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|IBILI, University of Coimbra, Coimbra, Portugal.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Seiça
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D009569:Nitric Oxide; D002784:Cholesterol