Published online before print January 2, 2009, doi: 10.1161/CIRCRESAHA.108.182998
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© 2009 American Heart Association, Inc.
Integrative Physiology |
Proinflammatory Phenotype of Perivascular Adipocytes
Influence of High-Fat Feeding
From the Department of Internal Medicine and the Veteran’s Administration Medical Center (T.K.C., A.H., A.L.B., G.I., F.G.R., B.N., N.L.W.) and Department of Surgery (S.R.), University of Cincinnati College of Medicine, Ohio; and Department of Emergency Medicine (L.L.S., G.M.D., S.A.R.-M., E.W.D.), University of Iowa Carver College of Medicine, Iowa City.
Correspondence to Dr Neal L. Weintraub, Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0542, Cincinnati, OH 45267-0542. E-mail neal.weintraub{at}uc.edu
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.
Key Words: perivascular adipose tissue • adipocytes • adventitia • adipokines • cytokines
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