Journal article

Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism

Graeme I Lancaster, Katherine G Langley, Nils Anton Berglund, Helene L Kammoun, Saskia Reibe, Emma Estevez, Jacquelyn Weir, Natalie A Mellett, Gerard Pernes, James RW Conway, Man KS Lee, Paul Timpson, Andrew J Murphy, Seth L Masters, Steve Gerondakis, Nenad Bartonicek, Dominik C Kaczorowski, Marcel E Dinger, Peter J Meikle, Peter J Bond Show all



Chronic inflammation is a hallmark of obesity and is linked to the development of numerous diseases. The activation of toll-like receptor 4 (TLR4) by long-chain saturated fatty acids (lcSFAs) is an important process in understanding how obesity initiates inflammation. While experimental evidence supports an important role for TLR4 in obesity-induced inflammation in vivo, via a mechanism thought to involve direct binding to and activation of TLR4 by lcSFAs, several lines of evidence argue against lcSFAs being direct TLR4 agonists. Using multiple orthogonal approaches, we herein provide evidence that while loss-of-function models confirm that TLR4 does, indeed, regulate lcSFA-induced inflammat..

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Awarded by National Health and Medical Research Council (NHMRC)

Funding Acknowledgements

This study was funded, in part, by the National Health and Medical Research Council (NHMRC project grant no. 586636 to M.A.F. and G.I.L.) and the Victorian Governments Operational Support Program. M.A.F. is a Senior Principal Research Fellow of the NHMRC (APP1116936). S.L.M. acknowledges funding from the Sylvia and Charles Viertel Foundation, HHMI-Wellcome International Research Scholarship, and Glaxosmithkline. We would also like to acknowledge the three anonymous reviewers for their constructive advice and suggestions.