Kartoffel
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Recently, there has been a lot of talk about saturated fat and the toll-like receptor proteins that are involved in immune reactions and the inflammatory cascade that follows their activation. People here on the forum and elsewhere have repeatedly cited several in vitro studies supposedly showing that saturated fatty acids serve as ligands for TLR2 and TLR4 (the one that is mostly activated by endotoxin). The story is that saturated fatty acids like palmitic, lauric, or stearic acid bind directly with the TLRs and are therefore inherently pro-inflammatory.
That would, in fact, be bad, if it were so. Luckily, these studies are, like so many, just more artefacts of scientific incompetence. As this paper shows, the saturated fatty acids do not stimulate TLR activation, even in massive quantities. As it turns out, the studies demonstrating TLR activation by saturated fatty acids used a reagent to complex with the fatty acids for use that was contaminated with significant quantities of LPS and bacterial lipopeptides. Both are known to act as ligands for TLR4 and induce inflammation.
The saturated fatty acids alone did not activate TLRs, at all, while bovine serum albumin (the reagent they used) activated the inflammatory response attributed to saturated fat. I'm not sure, if someone mentioned this study before, but since the claims about SFA and TLRs continue to pop up here, it thought it might be worth a thread.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1944-9.
Saturated fatty acids do not directly stimulate Toll-like receptor signaling.
Erridge C1, Samani NJ.
"Instead, we present evidence that fatty-acid–free BSA, the reagent used in previous studies to present SFAs to cells in a physiological form, can be contaminated with both LPS and lipopeptide, and therefore likely accounts for the results of these previous studies."
They further demonstrated that BSA alone strongly stimulated TLR4 and inflammatory cytokines like TNF-a. The effect was even more pronounced than for endotoxin alone.
That would, in fact, be bad, if it were so. Luckily, these studies are, like so many, just more artefacts of scientific incompetence. As this paper shows, the saturated fatty acids do not stimulate TLR activation, even in massive quantities. As it turns out, the studies demonstrating TLR activation by saturated fatty acids used a reagent to complex with the fatty acids for use that was contaminated with significant quantities of LPS and bacterial lipopeptides. Both are known to act as ligands for TLR4 and induce inflammation.
The saturated fatty acids alone did not activate TLRs, at all, while bovine serum albumin (the reagent they used) activated the inflammatory response attributed to saturated fat. I'm not sure, if someone mentioned this study before, but since the claims about SFA and TLRs continue to pop up here, it thought it might be worth a thread.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1944-9.
Saturated fatty acids do not directly stimulate Toll-like receptor signaling.
Erridge C1, Samani NJ.
"Instead, we present evidence that fatty-acid–free BSA, the reagent used in previous studies to present SFAs to cells in a physiological form, can be contaminated with both LPS and lipopeptide, and therefore likely accounts for the results of these previous studies."
"In a screen of a wide variety of cell types, including macrophages, adipocytes, smooth muscle cells, and endothelial cells, we found that SFAs did not induce expression of gene products that are typically upregulated by TLR-stimulation, such as IL-1 ,TNF-a ,CCL-2,andE-selectin. SFAs also did not promote the phosphorylation of p38 MAPK or degradation of which are established to be universal featuresof TLR-stimulation in macrophages. Finally, in transfected HEK-293 cells, which are sensitive to very low concentrations of respective TLR-ligands, SFAs, even at supraphysiological levels, neither induced nor enhanced TLR2 or TLR4 signaling"
The graph below shows the expression of TLR2, TLR4, and TLR4 after contact with SFA complexed with BSA (A-C), and without it (D-F)
They further demonstrated that BSA alone strongly stimulated TLR4 and inflammatory cytokines like TNF-a. The effect was even more pronounced than for endotoxin alone.
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