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

Abstract

The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1β/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1β using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1β 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 (V̇o2). V̇o2 dependent on metabolic thermogenesis (ΔV̇o2 thermogenesis) calculated by correcting the effect of physical activity was increased after IL-1β 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 ΔV̇o2 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 ΔV̇o2 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-1β-induced fever. In support of this, we found no effect of IL-1β on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243.