Proinflammatory cytokine interleukin-1 beta suppresses cold-induced thermogenesis in adipocytes

In this study, we investigated the effects of interleukin-1 beta (IL-1 beta), a typical proinflammatory cytokine on the beta-adrenoreceptor-stimulated induction of uncoupling protein 1 (UCP1) expression in adipocytes. IL-1 beta mRNA expression levels were upregulated in white adipose tissues of obese mice and in RAW264.7 macrophages under conditions designed to mimic obese adipose tissue. Isoproterenol-stimulated induction of UCP1 mRNA expression was significantly inhibited in C3H10T1/2 adipocytes by conditioned medium from lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in comparison with control conditioned medium. This inhibition was significantly attenuated in the presence of recombinant IL-1 receptor antagonist and IL-1 beta antibody, suggesting that activated macrophage-derived IL-1 beta is an important cytokine for inhibition of beta-adrenoreceptor-stimulated UCP1 induction in adipocytes. IL-1 beta suppressed isoproterenol-induced UCP1 mRNA expression in C3H10T1/2 adipocytes, and this effect was partially but significantly abrogated by inhibition of extracellular signal-regulated kinase (ERK). IL-1 beta also suppressed the isoproterenol-induced activation of the UCP1 promoter and transcription factors binding to the CAMP response element. Moreover, intraperitoneal administration of IL-1 beta suppressed cold-induced UCP1 expression in adipose tissues. These findings suggest that IL-1 beta upregulated in obese adipose tissues suppresses beta-adrenoreceptor-stimulated induction of UCP1 expression through ERK activation in adipocytes. (C) 2015 Elsevier Ltd. All rights reserved.