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TLR-3 Is Present in Human Adipocytes, but Its Signalling Is Not Required for Obesity-Induced Inflammation in Adipose Tissue in Vivo

TLR-3 Is Present in Human Adipocytes, but Its Signalling Is Not Required for Obesity-Induced Inflammation in Adipose Tissue in Vivo

Dov B Ballak, Edwin J P van Asseldonk, Janna A van Diepen, Henry Jansen, Anneke Hijmans, Leo A B Joosten, Cees J Tack, Mihai G Netea, Rinke Stienstra

PLoS One. 2015 Apr 13;10(4):e0123152.

PMID: 25867514

Abstract:

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 HFD-induced 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248888	TLR-3 human			Price

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