Systemic inflammation activates the nuclear factor-κB regulatory pathway in adipose tissue

Abstract

Adipose tissue (AT) is a store of energy but also an endocrine organ with the capacity to produce and release proinflammatory mediators into the circulation. The mechanism that may trigger human AT inflammation on a cellular level still remains largely unknown. The aim of this study was to investigate whether an acute systemic inflammation increases AT inflammatory activity, focused on innate immunity. Open heart surgery results in an extensive acute systemic inflammation. Therefore, we investigated the in vivo gene expression and production of inflammatory mediators in omental and subcutaneous AT stimulated by surgery. Biopsies from omental and subcutaneous AT were collected before and after cardiopulmonary bypass. Blood samples were collected at the same time as the AT biopsies and plasma IL-6 levels were measured with ELISA. RT-PCR was used for quantification of relative AT gene expression. To verify the gene expression results on a protein level, we used immunohistochemistry and microdialysis. After surgery, in both omental and subcutaneous AT, there was a strong upregulation of nuclear factor-kappaB-regulated genes, e.g., chemokine ligand-2, E-selectin, IL-1beta, IL-6, IL-8, and Toll-like receptor-2. Immunohistochemistry showed staining for E-selectin associated with a high number of macrophages in close contact with and in the vascular wall. Increased levels of IL-6 were detected in microdialysate from subcutaneous AT. In conclusion, we present the novel finding that this model of inflammation induced a strong inflammatory response in both omental and subcutaneous AT including adhesion of macrophages to an activated endothelium and release of IL-6 from AT interstitium. It can be hypothesized that AT exerts a modulatory effect on innate immunity in humans.

Coronary artery bypass graft surgery up‐regulates genes involved in platelet aggregation

“…Inflammatory mediators from surgery trauma, such as IL6, are associated with thrombocytosis [31], and work performed by our group and others has shown that after CABG there is a systemic increase in plasma IL6 [25,27]. Our results showed an increase in CRP levels and numbers of circulating leukocytes, both of which confirm a strong inflammatory reaction.…”

“…CABG surgery represents one of the strongest models of inflammation in humans and results in extensive acute inflammation. After CABG there is a huge increase in gene expression and plasma protein levels of inflammatory mediators such as tumor necrosis factor, interleukin (IL) 6 and IL1 [25–27]. This extreme inflammatory response might contribute to a number of post‐surgery complications, including thrombus formation and MI [9].…”

No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial

“…We also investigated a novel mechanism of adipose tissue inflammation involving the FFA chaperone protein fetuin-A (32). We hypothesized that adipose tissue inflammatory pathways could be triggered directly by fructose-induced systemic inflammation (11) or indirectly by fetuin-A activation of inflammatory pathways in adipose tissue (15). We measured several genes in adipose tissue known to be involved in the inflammatory process and quantified and characterized the activation state of immune cell populations isolated from the SVF in a comprehensive effort to detect any differential effect of the beverages on adipose tissue inflammation.…”

“…First, high fructose consumption, even under short-term isocaloric conditions, promotes the translocation of microbial material from the gut lumen to the portal circulation in rodents, thereby triggering low-grade hepatic and systemic inflammation (7,10). Because systemic inflammation can trigger the activation of inflammatory pathways in adipose tissue (11), we hypothesized that hepatic and systemic inflammation triggered by increased intestinal permeability and endotoxinemia may also result in changes in adipose tissue inflammation. Second, even under isocaloric conditions, substituting liquid fructose in place of solid carbohydrate foods resulted in considerably increased de novo lipogenesis (DNL) in the liver within just 9 d (12).…”

Effect of siRNA-induced inhibition of IL-6 expression in rat cerebral gliocytes on cerebral edema following traumatic brain injury

“…The interference effect 24 h after LPS induction was stronger than that 48 h after LPS induction, while the pSUPER empty plasmid had no effect. IL-6 and -8 expression is activated through the nuclear factor κ-light-chain-enhancer of activated B cell pathway, by IL-1β and TNF-α (35). In the present study, to investigate whether pSUPER-IL-6 transfection exerted a non-specific effect and affected IL-8 secretion, IL-8 protein levels were also assessed following transfection.…”