TLR-3 is present in human adipocytes, but its signalling is not required for obesity- Induced inflammation in adipose tissue in vivo

Innate immunity plays a pivotal role in obesity-induced low-grade inflammation originating from adipose tissue. Key receptors of the innate immune system including Toll-like receptors- 2 and -4 (TLRs) are triggered by nutrient excess to promote inflammation. The role of other TLRs in this process is largely unknown. In addition to double-stranded viral mRNA, TLR-3 can also recognize mRNA from dying endogenous cells, a process that is frequently observed within obese adipose tissue. Here, we identified profound expression of TLR-3 in adipocytes and investigated its role during diet-induced obesity. Human adipose tissue biopsies (n=80) and an adipocyte cell-line were used to study TLR-3 expression and function. TLR-3-/- and WT animals were exposed to a high-fat diet (HFD) for 16 weeks to induce obesity. Expression of TLR-3 was significantly higher in human adipocytes compared to the non-adipocyte cells part of the adipose tissue. In vitro, TLR-3 expression was induced during differentiation of adipocytes and stimulation of the receptor led to elevated expression of pro-inflammatory cytokines. In vivo, TLR-3 deficiency did not significantly influence HFDinduced obesity, insulin sensitivity or inflammation. In humans, TLR-3 expression in adipose tissue did not correlate with BMI or insulin sensitivity (HOMA-IR). Together, our results demonstrate that TLR-3 is highly expressed in adipocytes and functionally active. However, TLR-3 appears to play a redundant role in obesity-induced inflammation and insulin resistance.</p

TLR-3 is present in human adipocytes, but its signalling is not required for obesity- Induced inflammation in adipose tissue in vivo

<p>Innate immunity plays a pivotal role in obesity-induced low-grade inflammation originating from adipose tissue. Key receptors of the innate immune system including Toll-like receptors- 2 and -4 (TLRs) are triggered by nutrient excess to promote inflammation. The role of other TLRs in this process is largely unknown. In addition to double-stranded viral mRNA, TLR-3 can also recognize mRNA from dying endogenous cells, a process that is frequently observed within obese adipose tissue. Here, we identified profound expression of TLR-3 in adipocytes and investigated its role during diet-induced obesity. Human adipose tissue biopsies (n=80) and an adipocyte cell-line were used to study TLR-3 expression and function. TLR-3-/- and WT animals were exposed to a high-fat diet (HFD) for 16 weeks to induce obesity. Expression of TLR-3 was significantly higher in human adipocytes compared to the non-adipocyte cells part of the adipose tissue. In vitro, TLR-3 expression was induced during differentiation of adipocytes and stimulation of the receptor led to elevated expression of pro-inflammatory cytokines. In vivo, TLR-3 deficiency did not significantly influence HFDinduced obesity, insulin sensitivity or inflammation. In humans, TLR-3 expression in adipose tissue did not correlate with BMI or insulin sensitivity (HOMA-IR). Together, our results demonstrate that TLR-3 is highly expressed in adipocytes and functionally active. However, TLR-3 appears to play a redundant role in obesity-induced inflammation and insulin resistance.</p

The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation.

Contains fulltext : 88907.pdf (publisher's version ) (Closed access)Obesity is characterized by chronic low-grade inflammation originating from expanding adipose tissue. In the present study, we examined the adipogenic expression levels of IL-1F6 and IL-1F8, both members of the IL-1 family of cytokines, and their effects on adipose tissue gene expression. Although IL-1F6 is primarily present in adipose tissue resident macrophages and induced by inflammation, IL-1F8 is absent. IL-1F6, but not IL-1F8, reduces adipocyte differentiation, as shown by a significant decrease in PPARgamma gene expression. Finally, both IL-1F6 and IL-1F8 are able to induce inflammatory gene expression in mature adipocytes. In conclusion, we demonstrate for the first time that IL-1F6 is present in adipose tissue and that IL-1F6 and IL-1F8 are involved in the regulation of adipose tissue gene expression. Importantly, IL-1F6 inhibits PPARgamma expression which may lead to reduced adipocyte differentiation suggesting metabolic effects of this cytokine.1 november 201