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

ABSTRACT: 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?, a proinflammatory cytokine, is suggested to be involved in the development of insulin resistance. This study investigated the role of IL-1? 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? 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? mediates MC medium-induced alteration in adipocyte lipid storage. MC medium and IL-1? significantly reduced gene expression and protein abundance of insulin signaling molecules, including insulin receptor substrate-1, phosphoinositide 3-kinase p85?, 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? 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? neutralization. We conclude that IL-1? mediates, at least in part, the effect of macrophages on insulin signaling and proinflammatory response in human adipocytes. Blocking IL-1? could be beneficial for preventing obesity-associated insulin resistance and inflammation in human adipose tissue.

SUBMITTER: Gao D

PROVIDER: S-EPMC4121578 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Gao Dan D Madi Mohamed M Ding Cherlyn C Fok Matthew M Steele Thomas T Ford Christopher C Hunter Leif L Bing Chen C

American journal of physiology. Endocrinology and metabolism 20140610 3

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-1β, a proinflammatory cytokine, is suggested to be involved in the development of insulin resistance. This study investigated the ...[more]

PMID: 24918199

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

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

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