The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms

Abstract

Palmitic acid is a saturated fatty acid whose blood concentration is elevated in obese patients. This causes inflammatory responses, where toll-like receptors (TLR), TLR2 and TLR4, play an important role. Nevertheless, palmitic acid is not only a TLR agonist. In the cell, this fatty acid is converted into phospholipids, diacylglycerol and ceramides. They trigger the activation of various signaling pathways that are common for LPS-mediated TLR4 activation. In particular, metabolic products of palmitic acid affect the activation of various PKCs, ER stress and cause an increase in ROS generation. Thanks to this, palmitic acid also strengthens the TLR4-induced signaling. In this review, we discuss the mechanisms of inflammatory response induced by palmitic acid. In particular, we focus on describing its effect on ER stress and IRE1α, and the mechanisms of NF-κB activation. We also present the mechanisms of inflammasome NLRP3 activation and the effect of palmitic acid on enhanced inflammatory response by increasing the expression of FABP4/aP2. Finally, we focus on the consequences of inflammatory responses, in particular, the effect of TNF-α, IL-1β and IL-6 on insulin resistance. Due to the high importance of macrophages and the production of proinflammatory cytokines by them, this work mainly focuses on these cells.

Control the Mechanical Properties and Degradation of Poly(Glycerol Sebacate) by Substitution of the Hydroxyl Groups with Palmitates

“…A higher palmitate content would likely induce a strong inflammatory response to the materials which is adverse for the arterial remodeling. [ 48,49 ] According to the synergistic effects of the reduced elastic modulus, enhanced elasticity and slower degradation, we deduce that PPGS‐9 and PPGS‐16 could meet our requirements for small arteries. We have therefore used PPGS‐9 and PPGS‐16 together with PGS to construct vascular grafts for an in vivo study in a rat carotid model.…”

Annexin A1 Regulates NLRP3 Inflammasome Activation and Modifies Lipid Release Profile in Isolated Peritoneal Macrophages

“…PA acts as a lipid mediator in inflammation and its derived-metabolic products accumulate in the endoplasmic reticulum (ER) and increase reactive oxygen species (ROS) generation, leading to cell death [52]. Additionally, the inflammatory response caused by ER stress and ROS generation from high concentrations of PA drives NF-κB and NLRP3 activation and, consequently, proinflammatory cytokine release by monocytes/macrophages [53][54][55][56]. S-Acetyldihydrolipoamide, N-palmitoyl serine and PE(P-16:0/00) (2-Hexadecanoyl-1-(1Z-hexadecenyl)-sn-glycero-3-phosphoethanolamine) are associated with cell metabolism [57], membrane receptor [58], and cell membrane compounds [59], respectively.…”

Anethole dithiolethione improves liver fatty acid metabolism in hamster fed high-fat diets

“…When the increased intracellular PA level exceeds its βoxidation in mitochondria, it is converted to harmful complex lipids such as diacylglycerin (DAG) and ceramide (5,27). These harmful FA-derived intermediates and excessive PA provoke increased reactive oxygen species (ROS) production, damage the function of mitochondria-related ER membrane (MAM), and induce mitochondrial fragmentation, resulting in mitochondrial dysfunction and loss of ATP production (28)(29)(30)(31). Recently, Rambold et al reported that fragmented mitochondria failed to efficiently take up FA, causing a reduction in β-oxidation rates and further exacerbating the accumulation of FA in Mitofusin1 KO cells (15).…”