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

Okamatsu-Ogura Y, Kitao N, Kimura K, Saito M. Brown fat UCP1 is not involved in the febrile and thermogenic responses to IL-1 in mice. Am J Physiol Endocrinol Metab 292: E1135–E1139, 2007. First published December 12, 2006; doi:10.1152/ajpendo.00425.2006.—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 g/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 (V̇O2). V̇O2 dependent on metabolic thermogenesis ( V̇O2 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 V̇O2 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 V̇O2 in WT mice, showing 1,229 35 ml h 1 kg 1 of V̇O2 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.