Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages

Ann, Soo jin; Kim, Ka Kyung; Cheon, Eun Jung; Noh, Hye Min; Hwang, Inhwa; Yu, Je-Wook; Park, Sungha; Kang, Seok Min; Manabe, Ichiro; Miller, Yury I.; Kim, Sang Woo; Lee, Sang Hak

doi:10.1371/journal.pone.0193649

Cited by 9 publications

(14 citation statements)

References 36 publications

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“…As a consequence, TLR can be repeatedly activated during multi-day treatment of the cells with this SFA [87]. PA may increase the mRNA expression and protein levels of TLR4, which enhances the signal transduction of this receptor [129–131]. It can also support the activation of TLR4.…”

Section: Indirect Effect Of Palmitic Acid On Toll-like Receptors Actimentioning

confidence: 99%

“…As a consequence, in macrophages and monocytes, there is an increased expression of cytokines such as IL-1β [85], TNF-α [86, 88], CCL2/monocyte chemoattractant protein-1 (MCP-1) [91, 130, 182], CCL4/macrophage inflammatory protein 1β (MIP-1β) [183] and increase in COX-2 [84, 136] and matrix metallopeptidase 9 (MMP-9) expression [85, 92]. PA also increases the LPS effect on the IL-1β [130], CXCL2 [131] and TNF-α production [130, 131]. However, PA can also induce TNF-α expression independently of TLR4 activation [54].…”

Section: Consequences Of the Proinflammatory Action Of Palmitic Acidmentioning

confidence: 99%

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

2019

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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.

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Section: Indirect Effect Of Palmitic Acid On Toll-like Receptors Actimentioning

confidence: 99%

Section: Consequences Of the Proinflammatory Action Of Palmitic Acidmentioning

confidence: 99%

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

2019

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“…Indeed, the collected data showed that plasma lipid SFA level is positively correlated the plasma levels of the CRP, fibrinogen and pro-inflammatory cytokines [ 21 , 22 ]. In fact, SFA seem to stimulate inflammatory responses through immune cell effector activation and recruitment [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Saturated and Monounsaturated Fatty Acids in Behçet’s Disease

Messedi¹,

Naifar²,

Grayaa³

et al. 2018

TORJ

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Background:Fatty Acid (FA) composition of serum has been associated with many markers of inflammation. In this study, we tried to examine plasma Saturated Fatty Acid (SFA) and Monounsaturated Fatty Acid (MUFA) composition in Behçet's Disease (BD) patients. The associations between the circulating FA levels and some markers of inflammation have also been investigated.Methods:This study is a cross-sectional one. In fact, a total of 101 BD patients and healthy controls group of 99 subjects are enrolled. Gas Chromatograph equipped with a Capillary Split/Splitless Injector and flame ionization detector was used to analyze the plasma SFA and MUFA compositions. The high sensitivity C-Reactive Protein (hsCRP) and fibrinogen levels were measured using standard techniques.Results:BD patients had significantly higher proportions of Mystiric Acid (MA), Palmitic Acid (PAM), Palmitoleic Acid (POA) and Stearoyl-CoA Desaturase (SCD)-16, compared to controls.The results revealed that patients with severe involvements had high levels of POA and total MUFA associated with higher SCD-16 activity compared to those with minor ones. The receiver operator characteristic curve analysis revealed that POA could well discriminate BD patients with severe clinical manifestations. In the bivariate analysis, hsCRP was found to be positively correlated with total SAFA and POA elongase activity index but negatively correlated with SCD-18 activity index. The STA, POA, elongase and SCD-16 activity index are correlated with fibrinogen. On the other hand, the multivariate analysis showed that POA remained associated with higher levels of hsCRP.Conclusion:Unfavourable plasma SFA and MUFA profile were reported in BD patients. POA, which is associated with higher plasma hsCRP level, may play a role in the pathogenesis of BD.

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“…These, become much more responsive under physiologic stimuli which depend on the NLRP3-inflammasome pathway (Christ et al, 2018). Selective lipid species, such as palmitate and stearate, as well as, carbohydrates have been identified to activate the NLRP3inflammasome pathway (Wen et al, 2011;Ann et al, 2018). For instance, saturated lipids from diet intake such as palmitic and stearic acids promote IL-1β release from bone marrowderived macrophages of rodents and humans, respectively (Wen et al, 2011;L'homme et al, 2013), an effect replicated in murine macrophages (Ann et al, 2018).…”

Section: Potential Role Of the Nod-like Receptor Protein 3 Inflammasomentioning

confidence: 99%

“…Selective lipid species, such as palmitate and stearate, as well as, carbohydrates have been identified to activate the NLRP3inflammasome pathway (Wen et al, 2011;Ann et al, 2018). For instance, saturated lipids from diet intake such as palmitic and stearic acids promote IL-1β release from bone marrowderived macrophages of rodents and humans, respectively (Wen et al, 2011;L'homme et al, 2013), an effect replicated in murine macrophages (Ann et al, 2018). Of note, immune activation by palmitic and stearic acids precisely depends on the NLRP3-inflammasome pathway (Wen et al, 2011;L'homme et al, 2013).…”

Section: Potential Role Of the Nod-like Receptor Protein 3 Inflammasomentioning

confidence: 99%

Neurodegenerative Susceptibility During Maternal Nutritional Programing: Are Central and Peripheral Innate Immune Training Relevant?

et al. 2020

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Maternal overnutrition modulates body weight, development of metabolic failure and, potentially, neurodegenerative susceptibility in the offspring. Overnutrition sets a chronic pro-inflammatory profile that integrates peripheral and central immune activation nodes, damaging neuronal physiology and survival. Innate immune cells exposed to hypercaloric diets might experience trained immunity. Here, we address the role of maternal overnutrition as a trigger for central and peripheral immune training and its contribution to neurodegeneration and the molecular nodes implicated in the Nod-like receptor protein 3 (NLRP3) inflammasome pathway leading to immune training. We propose that maternal overnutrition leads to peripheral or central immune training that favor neurodegenerative susceptibility in the offspring.

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Palmitate and minimally-modified low-density lipoprotein cooperatively promote inflammatory responses in macrophages

Cited by 9 publications

References 36 publications

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

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

Plasma Saturated and Monounsaturated Fatty Acids in Behçet’s Disease

Neurodegenerative Susceptibility During Maternal Nutritional Programing: Are Central and Peripheral Innate Immune Training Relevant?

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