title: TLR-3 is present in human adipocytes, but its signalling is not required for obesity-induced inflammation in adipose tissue in vivo.
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.
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Dov B
authors: DB
authors: Ballak
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Edwin J P
authors: EJ
authors: van Asseldonk
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Janna A
authors: JA
authors: van Diepen
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Henry
authors: H
authors: Jansen
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Anneke
authors: A
authors: Hijmans
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Leo A B
authors: LA
authors: Joosten
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Cees J
authors: CJ
authors: Tack
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Mihai G
authors: MG
authors: Netea
authors: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Nutrition, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors: Rinke
authors: R
authors: Stienstra
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D000368:Aged; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3