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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/E1135    most recent 00425.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Okamatsu-Ogura, Y. Articles by Saito, M. Search for Related Content PubMed PubMed Citation Articles by Okamatsu-Ogura, Y. Articles by Saito, M.

Brown fat UCP1 is not involved in the febrile and thermogenic responses to IL-1 in mice

¹Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University; and ²Department of Nutrition, Graduate School of Nursing and Nutrition, Tenshi College, Sapporo, Japan

Submitted 18 August 2006 ; accepted in final form 8 December 2006

The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1 using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1 injection (5 µg/kg ip) increased body temperature (+1.82°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 (O₂). O₂ dependent on metabolic thermogenesis (O_{2 thermogenesis}) calculated by correcting the effect of physical activity was increased after IL-1 injection (726 ± 200 ml·h^–1·kg^–1 at 1 h). Almost the same responses were observed in UCP1-deficient mice, showing 638 ± 87 ml·h^–1·kg^–1 of O_{2 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 O₂ in WT mice, showing 1,229 ± 35 ml·h^–1·kg^–1 of O_{2 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-1-induced fever. In support of this, we found no effect of IL-1 on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243.

uncoupling protein-1; oxygen consumption; body temperature; knockout mouse; interleukin-1