title: Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding.
abstract: Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro-differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.
authors.affiliation: Department of Internal Medicine and the Veteran's Administration Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0542, USA.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Chatterjee
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Stoll
authors.forename: Gerene M
authors.initials: GM
authors.lastname: Denning
authors.forename: Allan
authors.initials: A
authors.lastname: Harrelson
authors.forename: Andra L
authors.initials: AL
authors.lastname: Blomkalns
authors.forename: Gila
authors.initials: G
authors.lastname: Idelman
authors.forename: Florence G
authors.initials: FG
authors.lastname: Rothenberg
authors.forename: Bonnie
authors.initials: B
authors.lastname: Neltner
authors.forename: Sara A
authors.initials: SA
authors.lastname: Romig-Martin
authors.forename: Eric W
authors.initials: EW
authors.lastname: Dickson
authors.forename: Steven
authors.initials: S
authors.lastname: Rudich
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
mesh_terms: D017667:Adipocytes / Q000276:immunology* / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics; D052242:Adiponectin / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000276:immunology; D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003238:Connective Tissue / Q000276:immunology* / Q000473:pathology; D003331:Coronary Vessels / Q000276:immunology; D004041:Dietary Fats / Q000009:adverse effects*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D050151:Subcutaneous Fat / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D018932:Chemokine CCL2; D004041:Dietary Fats; D050556:Fatty Acid-Binding Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D047495:PPAR gamma