Brown fat UCP1 is not involved in the febrile and thermogenic responses to IL-1beta in mice.
The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1beta/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1beta using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1beta injection (5 microg/kg ip) increased body temperature (+1.82 degrees C at 20 min), decreased physical activity (-37% at 1 h), and produced a slight and insignificant rise (+15% at 1 h) in oxygen consumption (Vo(2)). Vo(2) dependent on metabolic thermogenesis (DeltaVO2 thermogenesis) calculated by correcting the effect of physical activity was increased after IL-1beta injection (726 +/- 200 ml x h(-1) x kg(-1) at 1 h). Almost the same responses were observed in UCP1-deficient mice, showing 638 +/- 87 ml x h(-1) x kg(-1) of DeltaVO2 thermogenesis at 1 h. In contrast, CL316,243, a selective activator of BAT thermogenesis, increased body temperature, decreased physical activity, and produced a significant rise in Vo2 in WT mice, showing 1,229 +/- 35 ml x h(-1) x kg(-1) of DeltaVO2 thermogenesis at 1 h. These changes were not observed in UCP1-deficient mice. These results, conflicting with a previously proposed idea of a role of BAT in fever, suggest a minor contribution of BAT thermogenesis to IL-1beta-induced fever. In support of this, we found no effect of IL-1beta on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243.
Okamatsu-Ogura
Yuko
Y
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Japan.
Kitao
Naoya
N
Kimura
Kazuhiro
K
Saito
Masayuki
M
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology*; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism; D000071256:Uncoupling Protein 1
D053583:Interleukin-1beta; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1