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Bioactive Lipids in Inflammatory Diseases

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioactive Lipids".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 13148

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Special Issue Editors

Prof. Dr. Mauro Maccarrone

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1. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
2. European Center for Brain Research, Santa Lucia Foundation IRCCS, Rome, Italy
Interests: arachidonate cascade; bioactive lipids; biomarkers; cell membranes; endocannabinoids; resolvins; signal transduction
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Eva de Lago Femia

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Instituto de Investigación en Neuroquímica, Departamento de Bioquímica y Biología Molecular, Universidad Complutense de Madrid, Madrid, Spain
Interests: endocannabinoids; neuroprotective compounds; inflammation; lipids mediators; biomarkers; kinase inhibitors

Prof. Dr. Jesmond Dalli

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William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
Interests: resolution biology; lipid mediators; inflammation; identification of functional biomarkers; leukocyte biology

Special Issue Information

Dear Colleagues,

Lipids play a diverse function in biology ranging from structural roles to energy depots and signalling molecules. Recent years have seen an increased understanding of the role that these molecules play in a range of inflammatory conditions. Of particular interest in this context are lipid molecules that carry signalling functions. It is now increasingly appreciated that these compounds act as early signals to propagate inflammation, and as modulators of the acute inflammatory response to limit its propagation and facilitate its termination and the restitution of tissue and organ function. A key aspect in the biology of such signalling molecules is stereochemistry, which confers their bioactive properties. This is because in modulating the inflammatory response these molecules activate or modulate the activity of cognate receptors in target cells, thereby activating intracellular transduction pathways. Via these processes, bioactive lipids have been implicated in the regulation of cytokine production and cellular metabolism. In turn, these molecules and processes are also known to impinge on the production of bioactive lipids, providing tightly controlled signalling pathways. Mounting evidence suggests that highly coordinated processes become dysregulated in disease, contributing to both the onset and perpetuation of inflammation, as well as disease chronicity. Of note, lipids play many physiological functions within the brain, where they impact on structural integrity, impulse conduction, myelin sheath formation, fuel source, and signal transduction. Lipid metabolism is also important for the proper function and development of the brain, where the highest concentration of lipids in the body occurs, after adipose tissue; thus, dysregulation of lipid signalling may be of relevance for brain disorders or injuries, as well as for neurodegenerative/neuroinflammatory conditions such as Huntington´s chorea, Parkinson´s diseases, multiple sclerosis, or amyotrophic lateral sclerosis. The scope of the present Special Issue is to bring together the wealth of knowledge related to the role of bioactive lipids in the maintenance of health, both within the central nervous system and at the periphery, and how disruptions in the production and activity of these molecules may be linked with diseases characterized by uncontrolled inflammation.

Prof. Dr. Mauro Maccarrone
Prof. Dr. Eva de Lago Femia
Prof. Dr. Jesmond Dalli
Guest Editors

Manuscript Submission Information

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Keywords

eicosanoids
endocannabinoids
GPCR
metabolism
specialized pro-resolving mediators

Published Papers (6 papers)

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14 pages, 2482 KiB

Open AccessArticle

Differential Lipid Accumulation on HepG2 Cells Triggered by Palmitic and Linoleic Fatty Acids Exposure

by Francisca S. Teixeira, Lígia L. Pimentel, Susana S. M. P. Vidigal, João Azevedo-Silva, Manuela E. Pintado and Luís M. Rodríguez-Alcalá

Molecules 2023, 28(5), 2367; https://doi.org/10.3390/molecules28052367 - 04 Mar 2023

Cited by 5 | Viewed by 2438

Abstract

Lipid metabolism pathways such as β-oxidation, lipolysis and, lipogenesis, are mainly associated with normal liver function. However, steatosis is a growing pathology caused by the accumulation of lipids in hepatic cells due to increased lipogenesis, dysregulated lipid metabolism, and/or reduced lipolysis. Accordingly, this investigation hypothesizes a selective in vitro accumulation of palmitic and linoleic fatty acids on hepatocytes. After assessing the metabolic inhibition, apoptotic effect, and reactive oxygen species (ROS) generation by linoleic (LA) and palmitic (PA) fatty acids, HepG2 cells were exposed to different ratios of LA and PA to study the lipid accumulation using the lipophilic dye Oil Red O. Lipidomic studies were also carried out after lipid isolation. Results revealed that LA was highly accumulated and induced ROS production when compared to PA. Lipid profile modifications were observed after LA:PA 1:1 (v/v) exposure, which led to a four-fold increase in triglycerides (TGs) (mainly in linoleic acid-containing species), as well as a increase in cholesterol and polyunsaturated fatty acids (PUFA) content when compared to the control cells. The present work highlights the importance of balancing both PA and LA fatty acids concentrations in HepG2 cells to maintain normal levels of free fatty acids (FFAs), cholesterol, and TGs and to minimize some of the observed in vitro effects (i.e., apoptosis, ROS generation and lipid accumulation) caused by these fatty acids. Full article

(This article belongs to the Special Issue Bioactive Lipids in Inflammatory Diseases)

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15 pages, 2242 KiB

Open AccessArticle

Effect of Sphingomyelinase-Treated LDLs on HUVECs

by Angelica Giuliani, Camilla Morresi, Gabriele Mazzuferi, Luisa Bellachioma, Deborah Ramini, Jacopo Sabbatinelli, Fabiola Olivieri, Tiziana Bacchetti and Gianna Ferretti

Molecules 2023, 28(5), 2100; https://doi.org/10.3390/molecules28052100 - 23 Feb 2023

Viewed by 1213

Abstract

Low-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative modification has been mainly investigated as a major risk factor for accelerating atherogenesis. Since LDL sphingolipids are also emerging as important regulators of the atherogenic process, increasing attention is devoted to the effects of sphingomyelinase (SMase) on LDL structural and atherogenic properties. The aims of the study were to investigate the effect of SMase treatment on the physical-chemical properties of LDLs. Moreover, we evaluated cell viability, apoptosis, and oxidative and inflammatory status in human umbilical vein endothelial cells (HUVECs) treated with either ox-LDLs or SMase-treated LDLs (SMase-LDLs). Both treatments were associated with the accrual of the intracellular ROS and upregulation of the antioxidant Paraoxonase 2 (PON2), while only SMase-LDLs induced an increase of superoxide dismutase 2 (SOD2), suggesting the activation of a feedback loop to restrain the detrimental effects of ROS. The increased caspase-3 activity and reduced viability observed in cells treated with SMase-LDLs and ox-LDLs suggest a pro-apoptotic effect of these modified lipoproteins on endothelial cells. Moreover, a strong proinflammatory effect of SMase-LDLs compared to ox-LDLs was confirmed by an increased activation of NF-κB and consequent increased expression of its downstream cytokines IL-8 and IL-6 in HUVECs. Full article

(This article belongs to the Special Issue Bioactive Lipids in Inflammatory Diseases)

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11 pages, 1702 KiB

Open AccessArticle

Influence of Dietary n-3 Long Chain Polyunsaturated Fatty Acid Intake on Oxylipins in Erythrocytes of Women with Rheumatoid Arthritis

by Helen M. Lindqvist, Anna Winkvist, Inger Gjertsson, Philip C. Calder, Aaron M. Armando, Oswald Quehenberger, Roxana Coras and Monica Guma

Molecules 2023, 28(2), 717; https://doi.org/10.3390/molecules28020717 - 11 Jan 2023

Cited by 2 | Viewed by 1886

Abstract

Oxylipins derived from n-3 fatty acids are suggested as the link between these fatty acids and reduced inflammation. The aim of the present study was to explore the effect of a randomized controlled cross-over intervention on oxylipin patterns in erythrocytes. Twenty-three women with rheumatoid arthritis completed 2 × 11-weeks exchanging one cooked meal per day, 5 days a week, for a meal including 75 g blue mussels (source for n-3 fatty acids) or 75 g meat. Erythrocyte oxylipins were quantified by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The results were analyzed with multivariate data analysis. Orthogonal projections to latent structures (OPLS) with effect projections and with discriminant analysis were performed to compare the two diets’ effects on oxylipins. Wilcoxon signed rank test was used to test pre and post values for each dietary period as well as post blue-mussel vs. post meat. The blue-mussel diet led to significant changes in a few oxylipins from the precursor fatty acids arachidonic acid and dihomo-ɣ-linolenic acid. Despite significant changes in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and free EPA in erythrocytes in the mussel group, no concurrent changes in their oxylipins were seen. Further research is needed to study the link between n-3 fatty-acid intake, blood oxylipins, and inflammation. Full article

(This article belongs to the Special Issue Bioactive Lipids in Inflammatory Diseases)

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18 pages, 3737 KiB

Open AccessArticle

Effect of Structured Phenolic Lipids with EPA/DHA and Gallic Acid against Metabolic-Associated Fatty Liver Disease (MAFLD) in Mice

by Gretel Dovale-Rosabal, Alejandra Espinosa, Alicia Rodríguez, Andrés Barriga, Alan Palomino-Calderón, Nalda Romero, Rodrigo Hernán Troncoso and Santiago Pedro Aubourg

Molecules 2022, 27(22), 7702; https://doi.org/10.3390/molecules27227702 - 09 Nov 2022

Cited by 2 | Viewed by 1524

Abstract

Obesity is the leading risk factor for developing metabolic (dysfunction)-associated fatty liver disease (MAFLD). The food industry has an essential role in searching for new strategies to improve primary food sources to revert some of the metabolic alterations induced by obesity. There is consistent evidence that long-chain polyunsaturated fatty acids (n-3 LCPUFA) belonging to the n-3 series, i.e., eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) acids, could revert some alterations associated with obesity-induced metabolic diseases. A relevant tool is the synthesis of structured acylglycerols (sAG), which include EPA or DHA at the sn-2 position. On the other hand, it has been reported that a crucial role of antioxidants is the reversion of MAFLD. In this work, we studied the effects of new molecules incorporating gallic acid (GA) into EPA/DHA-rich structured lipids. Mice were fed with a high-fat diet (60%) for three months and were then divided into five groups for supplementation with sAG and sAG structured with gallic acid (structured phenolic acylglycerols, sPAG). sPAG synthesis was optimized using a 2²-screening factorial design based on the response surface methodology (RSM). Our results show that treatment of sPAG was effective in decreasing visceral fat, fasting glycemia, fasting insulin, suggesting that this new molecule has a potential use in the reversal of MAFLD-associated alterations. Full article

(This article belongs to the Special Issue Bioactive Lipids in Inflammatory Diseases)

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14 pages, 3801 KiB

Open AccessArticle

Sophorolipid Suppresses LPS-Induced Inflammation in RAW264.7 Cells through the NF-κB Signaling Pathway

by Ruiqi Xu, Ling Ma, Timson Chen and Jing Wang

Molecules 2022, 27(15), 5037; https://doi.org/10.3390/molecules27155037 - 08 Aug 2022

Cited by 15 | Viewed by 3625

Abstract

Objectives: Biosurfactants with anti-inflammatory activity may alleviate skin irritation caused by synthetic surfactants in cleaning products. Sophorolipid (SL) is a promising alternative to synthetic surfactants. However, there are few reports on the anti-inflammatory activity of SL and the underlying mechanism. The purpose of this work is to verify that lipopolysaccharide (LPS)-induced inflammation could be inhibited through targeting the pathway of nuclear factor-κB (NF-κB) in RAW264.7 cells. Methods: The influence of SL on cytokine release was investigated by LPS-induced RAW264.7 cells using ELISA. The quantification of the protein expression of corresponding molecular markers was realized by Western blot analysis. Flow cytometry was employed to determine the levels of Ca²⁺ and reactive oxygen species (ROS). The relative expression of inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX-2) was determined by RT-PCR. An immunofluorescence assay and confocal microscope were used to observe the NF-κB/p65 translocation from the cytoplasm into the nucleus. The likely targets of SL were predicted by molecular docking analysis. Results: SL showed anti-inflammatory activity and reduced the release of inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). The experimental results show that SL suppressed the Ca²⁺ and ROS levels influx in the LPS-induced RAW264.7 cells and alleviated the LPS-induced expression of iNOS and COX-2, the LPS-induced translocation of NF-κB (p65) from the cytoplasm into the nucleus, and the expression of phosphorylated proteins such as p65 and IκBα. Furthermore, molecular docking analysis showed that SL may inhibit inflammatory signaling by competing with LPS to bind TLR4/MD-2 through hydrophobic interactions and by inhibiting IKKβ activation through the hydrogen bonding and hydrophobic interactions. Conclusion: This study demonstrated that SL exerted anti-inflammatory activity via the pathway of NF-κB in RAW264.7 cells. Full article

(This article belongs to the Special Issue Bioactive Lipids in Inflammatory Diseases)

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13 pages, 2080 KiB

Open AccessPerspective

Deciphering Complex Interactions in Bioactive Lipid Signaling

by Mauro Maccarrone

Molecules 2023, 28(6), 2622; https://doi.org/10.3390/molecules28062622 - 14 Mar 2023

Cited by 4 | Viewed by 1529

Abstract

Lipids are usually viewed as metabolic fuel and structural membrane components. Yet, in recent years, different families of lipids able to act as authentic messengers between cells and/or intracellularly have been discovered. Such lipid signals have been shown to exert their biological activity via specific receptors that, by triggering distinct signal transduction pathways, regulate manifold pathophysiological processes in our body. Here, endogenous bioactive lipids produced from arachidonic acid (AA) and other poly-unsaturated fatty acids will be presented, in order to put into better perspective the relevance of their mutual interactions for health and disease conditions. To this end, metabolism and signal transduction pathways of classical eicosanoids, endocannabinoids and specialized pro-resolving mediators will be described, and the intersections and commonalities of their metabolic enzymes and binding receptors will be discussed. Moreover, the interactions of AA-derived signals with other bioactive lipids such as shingosine-1-phosphate and steroid hormones will be addressed. Full article

(This article belongs to the Special Issue Bioactive Lipids in Inflammatory Diseases)

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