title: Accelerated recovery from acute hypoxia in obese mice is due to obesity-associated up-regulation of interleukin-1 receptor antagonist.
abstract: The proinflammatory consequences of obesity are thought to be due, in part, to macrophage infiltration into adipose tissue. There are, however, potential antiinflammatory consequences of obesity that include obesity-associated up-regulation of IL-1 receptor antagonist (IL-1RA). Here we show that obesity-associated up-regulation of IL-1RA speeds recovery from hypoxia. We found that high-fat diet-fed (HFD) mice recovered from acute hypoxia 5 times faster than normal-diet-fed (ND) mice. HFD mice had a 10-fold increase in serum IL-1RA when compared with ND mice. White adipose tissue (WAT) was a significant source of IL-RA, generating 330 +/- 77 pg/mg protein in HFD mice as compared with 15 +/- 5 pg/mg protein in ND mice. Peritoneal macrophages isolated from HFD mice showed little difference in IL-1RA production when compared with ND mice, but WAT macrophages from HFD mice generated 11-fold more IL-1RA than those from ND mice. When ND mice were given an ip transfer of the stromal vascular fraction portion of WAT from HFD mice, serum IL-1RA increased 836% and recovery from acute hypoxia was faster than in mice that did not receive a stromal vascular fraction transfer. To determine whether IL-1RA was important to this accelerated recovery, ND mice were administered exogenous IL-1RA prior to hypoxia, and their recovery matched that of HFD mice. Inversely, when IL-1RA was immunoabsorbed in HFD mice with IL-1RA antiserum, recovery from acute hypoxia was attenuated. Taken together these data demonstrate that HFD-induced obesity speeds recovery from hypoxia due to obesity-associated up-regulation of IL-1RA.
authors.affiliation: Division of Nutritional Sciences, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Sherry
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Kim
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Freund
mesh_terms: D000208:Acute Disease; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000503:physiopathology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1