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

PLoS One. 2015 Apr 13;10(4):e0123152. doi: 10.1371/journal.pone.0123152. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipose Tissue / pathology*
  • Adult
  • Aged
  • Animals
  • Diet, High-Fat
  • Female
  • Humans
  • Inflammation / complications*
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Obesity / complications*
  • Signal Transduction*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism*
  • Weight Gain

Substances

  • TLR3 protein, human
  • Toll-Like Receptor 3

Grant support

RS was supported by a Ruby Grant of the Dutch Diabetes Research Foundation (http://www.diabetesfonds.nl). MN was supported by a Vici Grant from the Netherlands Organization for Scientific Research (NWO) (http://www.nwo.nl/financiering/onze-financieringsinstrumenten/nwo/vernieuwingsimpuls/vici/index.html) (http://www.nwo.nl/onderzoek-en-resultaten/programmas/vernieuwingsimpuls/toekenningen/alle+vici+toekenningen/Toekenningen+Vici+2009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.