当前位置： SCI文献检索 > ENDOCRINOLOGY期刊下所有文献 > Implication of the Tpl2 kinase in inflammatory changes and insulin resistance induced by the interaction between adipocytes and macrophages.

Implication of the Tpl2 kinase in inflammatory changes and insulin resistance induced by the interaction between adipocytes and macrophages.

Abstract：

:Adipose tissue inflammation is associated with the development of insulin resistance. In obese adipose tissue, lipopolysaccharides (LPSs) and saturated fatty acids trigger inflammatory factors that mediate a paracrine loop between adipocytes and macrophages. However, the inflammatory signaling proteins underlying this cross talk remain to be identified. The mitogen-activated protein kinase kinase kinase tumor progression locus 2 (Tpl2) is activated by inflammatory stimuli, including LPS, and its expression is up-regulated in obese adipose tissue, but its role in the interaction between adipocytes and macrophages remains ill-defined. To assess the implication of Tpl2 in the cross talk between these 2 cell types, we used coculture system and conditioned medium (CM) from macrophages. Pharmacological inhibition of Tpl2 in the coculture markedly reduced lipolysis and cytokine production and prevented the decrease in adipocyte insulin signaling. Tpl2 knockdown in cocultured adipocytes reduced lipolysis but had a weak effect on cytokine production and did not prevent the alteration of insulin signaling. By contrast, Tpl2 silencing in cocultured macrophages resulted in a marked inhibition of cytokine production and prevented the alteration of adipocyte insulin signaling. Further, when Tpl2 was inhibited in LPS-activated macrophages, the produced CM did not alter adipocyte insulin signaling and did not induce an inflammatory response in adipocytes. By contrast, Tpl2 silencing in adipocytes did not prevent the deleterious effects of a CM from LPS-activated macrophages. Together, these data establish that Tpl2, mainly in macrophages, is involved in the cross talk between adipocytes and macrophages that promotes inflammatory changes and alteration of insulin signaling in adipocytes.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Ceppo F,Berthou F,Jager J,Dumas K,Cormont M,Tanti JF

doi

10.1210/en.2013-1815

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

951-64

issue

eissn

0013-7227

issn

1945-7170

journal_volume

155

pub_type

杂志文章

在线工具

Implication of the Tpl2 kinase in inflammatory changes and insulin resistance induced by the interaction between adipocytes and macrophages.