Interleukin-1β mediates macrophage-induced impairment of insulin signaling in human primary adipocytes

Adipose tissue expansion during obesity is associated with increased macrophage infiltration. Macrophage- derived factors significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. Identification of the major factors that mediate detrimental effects of macrophages on adipocytes may offer potential therapeutic targets. IL-1 beta, a proinflammatory cytokine, is suggested to be involved in the development of insulin resistance. This study investigated the role of IL-1 beta in macrophage-adipocyte cross-talk, which affects insulin signaling in human adipocytes. Using macrophage-conditioned (MC) medium and human primary adipocytes, we examined the effect of IL-1 beta antagonism on the insulin signaling pathway. Gene expression profile and protein abundance of insulin signaling molecules were determined, as was the production of proinflammatory cytokine/chemokines. We also examined whether IL-1 beta mediates MC medium-induced alteration in adipocyte lipid storage. MC medium and IL-1 beta significantly reduced gene expression and protein abundance of insulin signaling molecules, including insulin receptor substrate-1, phosphoinositide 3-kinase p85 alpha, and glucose transporter 4 and phosphorylation of Akt. In contrast, the expression and release of the proinflammatory markers, including IL-6, IL-8, monocyte chemotactic protein-1, and chemokine (C-C motif) ligand 5 by adipocytes were markedly increased. These changes were significantly reduced by blocking IL-1 beta activity, its receptor binding, or its production by macrophages. MC medium-inhibited expression of the adipogenic factors and -stimulated lipolysis was also blunted with IL-1 beta neutralization. We conclude that IL-1 beta mediates, at least in part, the effect of macrophages on insulin signaling and proinflammatory response in human adipocytes. Blocking IL-1 beta could be beneficial for preventing obesity-associated insulin resistance and inflammation in human adipose tissue.