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 inflammation, TLR4 is not a receptor for lcSFAs. Rather, we show that TLR4-dependent priming alters cellular metabolism, gene expression, lipid metabolic pathways, and membrane lipid composition, changes that are necessary for lcSFA-induced inflammation. These results reconcile previous discordant observations and challenge the prevailing view of TLR4's role in initiating obesity-induced inflammation.
Pubmed ID: 29681442 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Phospho-eIF2 alpha (Ser51)
View all literature mentionsThis monoclonal targets CD284
View all literature mentionsThis monoclonal targets TLR4 MD2 Complex
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis polyclonal targets Rat IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets PYCARD
View all literature mentionsThis polyclonal targets caspase-1 p10
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis polyclonal targets eIF2 alpha
View all literature mentionsThis monoclonal targets NF-κB p65
View all literature mentionsThis unknown targets SEK1 / MKK4
View all literature mentionsThis monoclonal targets SEK1 / MKK, phospho (Ser257)
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis monoclonal targets Phospho-eIF2 alpha (Ser51)
View all literature mentions