beta3-Adrenergic receptor stimulation induces E-selectin-mediated adipose tissue inflammation
Program in Molecular Medicine
Adipose Tissue; Animals; 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
Cellular and Molecular Physiology | Endocrinology | Molecular Biology
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.
Adipose Tissue, Adipose Tissue Metabolism, Adrenergic Receptor, Endothelial Cell, Inflammation, Lipolysis, E-Selectin
DOI of Published Version
J Biol Chem. 2013 Jan 25;288(4):2882-92. doi: 10.1074/jbc.M112.412346. Link to article on publisher's site
The Journal of biological chemistry
Roth Flach, Rachel J.; Matevossian, Anouch; Akie, Thomas E.; Negrin, Kimberly A.; Paul, Marina T.; and Czech, Michael P., "beta3-Adrenergic receptor stimulation induces E-selectin-mediated adipose tissue inflammation" (2013). University of Massachusetts Medical School Faculty Publications. 203.