beta3-Adrenergic receptor stimulation induces E-selectin-mediated adipose tissue inflammation
Authors
Roth Flach, Rachel J.Matevossian, Anouch
Akie, Thomas E.
Negrin, Kimberly A.
Paul, Marina T.
Czech, Michael P.
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2013-01-25Keywords
Adipose TissueAnimals
Chemokine CCL2
Diabetes Mellitus, Type 2
E-Selectin
Human Umbilical Vein Endothelial Cells
Humans
Immune System
Inflammation
Interleukin-1beta
Lipolysis
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
Receptors, Adrenergic, beta-3
Tumor Necrosis Factor-alpha
Adipose Tissue
Adipose Tissue Metabolism
Adrenergic Receptor
Endothelial Cell
Inflammation
Lipolysis
E-Selectin
Cellular and Molecular Physiology
Endocrinology
Molecular Biology
Metadata
Show full item recordAbstract
Inflammation induced by wound healing or infection activates local vascular endothelial cells to mediate leukocyte rolling, adhesion, and extravasation by up-regulation of leukocyte adhesion molecules such as E-selectin and P-selectin. Obesity-associated adipose tissue inflammation has been suggested to cause insulin resistance, but weight loss and lipolysis also promote adipose tissue immune responses. While leukocyte-endothelial interactions are required for obesity-induced inflammation of adipose tissue, it is not known whether lipolysis-induced inflammation requires activation of endothelial cells. Here, we show that beta(3)-adrenergic receptor stimulation by CL 316,243 promotes adipose tissue neutrophil infiltration in wild type and P-selectin-null mice but not in E-selectin-null mice. Increased expression of adipose tissue cytokines IL-1beta, CCL2, and TNF-alpha in response to CL 316,243 administration is also dependent upon E-selectin but not P-selectin. In contrast, fasting increases adipose-resident macrophages but not neutrophils, and does not activate adipose-resident endothelium. Thus, two models of lipolysis-induced inflammation induce distinct immune cell populations within adipose tissue and exhibit distinct dependences on endothelial activation. Importantly, our results indicate that beta(3)-adrenergic stimulation acts through up-regulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration.Source
J Biol Chem. 2013 Jan 25;288(4):2882-92. doi: 10.1074/jbc.M112.412346. Link to article on publisher's siteDOI
10.1074/jbc.M112.412346Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29822PubMed ID
23235150Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M112.412346