Behavioral recovery from acute hypoxia is reliant on leptin.
Individuals affected by hypoxia experience a variety of immune-associated sickness symptoms including malaise, fatigue, lethargy and loss of interest in the physical and social environment. Recently, we demonstrated that the interleukin (IL)-1beta arm of the neuroimmune system was critical to the sickness symptoms caused by hypoxia, and that IL-1 receptor antagonist (IL-1RA), IL-1beta's endogenous inhibitor, was critical to promoting sickness recovery. Here, we report that leptin is key to recovery from hypoxia because it dramatically augmented IL-1RA production in mice. We found that hypoxia increased leptin in white adipose tissue (WAT) which in turn, caused a marked rise in serum IL-1RA. Interestingly, in-vitro, leptin was a more potent inducer of IL-RA, in macrophages, than hypoxia. In leptin receptor defective (db/db) and leptin deficient (ob/ob) mice, sickness recovery from hypoxia was delayed 3-fold. Importantly, in ob/ob mice, leptin administration completely reversed this delayed recovery and induced a marked increase in serum IL-1RA. Finally, leptin administration to normal mice reduced hypoxia recovery time by 1/3 and dramatically increased WAT and serum IL-1RA. Leptin did not alter recovery from hypoxia in IL-1RA knock out mice. These results show that by enhancing IL-1RA production leptin promoted sickness recovery from hypoxia.
Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
Christina L
CL
Sherry
Jason M
JM
Kramer
Jason M
JM
York
Gregory G
GG
Freund
D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000860:Hypoxia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000494:pharmacology* / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009068:Movement / Q000187:drug effects / Q000502:physiology; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics; D013997:Time Factors
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D020738:Leptin; D054411:Receptors, Leptin