β3-Adrenergic receptor stimulation induces E-selectin-mediated adipose tissue inflammation

J Biol Chem. 2013 Jan 25;288(4):2882-92. doi: 10.1074/jbc.M112.412346. Epub 2012 Dec 12.

Abstract

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 β(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-1β, CCL2, and TNF-α 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 β(3)-adrenergic stimulation acts through up-regulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology*
  • Animals
  • Chemokine CCL2 / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • E-Selectin / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immune System
  • Inflammation
  • Interleukin-1beta / metabolism
  • Lipolysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / metabolism
  • Receptors, Adrenergic, beta-3 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • E-Selectin
  • Interleukin-1beta
  • Receptors, Adrenergic, beta-3
  • Tumor Necrosis Factor-alpha