title: Eosinophils are key regulators of perivascular adipose tissue and vascular functionality.
abstract: Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function.
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Withers
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Forman
authors.affiliation: Immunology section, Lund University, BMC D14, SE-22184 Lund, Sweden.|University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Selene
authors.initials: S
authors.lastname: Meza-Perez
authors.affiliation: Immunology section, Lund University, BMC D14, SE-22184 Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sorobetea
authors.affiliation: Section for Immunology and Vaccinology, Danish Technical University, Veterinary Institute, Bülowsvej 27, DK-1870, Copenhagen, Denmark.
authors.forename: Kasia
authors.initials: K
authors.lastname: Sitnik
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hopwood
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Lawrence
authors.affiliation: Immunology section, Lund University, BMC D14, SE-22184 Lund, Sweden.|Section for Immunology and Vaccinology, Danish Technical University, Veterinary Institute, Bülowsvej 27, DK-1870, Copenhagen, Denmark.
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
authors.affiliation: Immunology section, Lund University, BMC D14, SE-22184 Lund, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Svensson-Frej
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Sheena M
authors.initials: SM
authors.lastname: Cruickshank
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D059305:Diet, High-Fat; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D002395:Catecholamines; D022702:Receptors, Adrenergic, beta-3; D009569:Nitric Oxide