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

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Scopus)

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 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.

Original languageEnglish
Article numbere0123152
JournalPLoS ONE
Volume10
Issue number4
DOIs
Publication statusPublished - 2015

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