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Advanced Research on Lipid Signaling Molecules
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Advanced Research on Lipid Signaling Molecules

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 November 2025 | Viewed by 9185

Special Issue Editor

Dr. Roberta Ottria

E-Mail Website
Guest Editor
Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, 20157 Milan, Italy
Interests: endocannabinoid system; endocannabinoid quantification; endocannabinoid hydrolytic enzymes; extracellular (EC) hydrolytic enzyme inhibitor synthesis and characterization; monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and N-acetylethanolamine hydrolyzing acid amidase (NAAA) activity evaluation methods; medicinal chemistry and biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipids are a key player in both extracellular and intracellular signaling in normal physiology and control numerous cellular processes, such as cell proliferation, apoptosis, metabolism, and migration, in a wide variety of tissues and cell types. Lipid signaling dysregulation contributes to inflammation, cancer, and metabolic, cardiovascular, and degenerative disease. Research promotes lipid signaling molecules being used as pharmacological tools, diagnostic or prognostic biomarkers, and, in some cases, functional nutrients and promotes their metabolic pathways as pharmacological targets. Considering the structurally diverse group of compounds composing lipid signaling molecules, such as free fatty acids, and fatty acid derivatives, such as oxylipins and eicosanoids, endocannabinoids, sphingolipids, phospholipids, and steroids, and their involvement in a wide range of physio-pathological processes, scientific research production in this area is striking.

The aim of this Special Issue is to focus on the lipid signaling molecules linked to the endocannabinoid signaling system, comprising endocannabinoids, free fatty acids, eicosanoids, and oxylipins derived from arachidonic, docosahexaenoic, and eicosatetraenoic acids, such as prostaglandins, leukotrienes, tromboxanes, resolvins, maresins, and protectins. Original research and review articles covering all aspects—such as the quantification of biomatrices in physiological and/or pathological conditions, tone modulation by enzyme activity modulation, and signaling biochemical pathways—of these families of lipid signaling molecules will be considered for publication.

Dr. Roberta Ottria
Guest Editor

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Keywords

  • endocannabinoid hydrolytic enzyme inhibitors
  • endocannabinoids
  • oxylipins
  • eicosanoids
  • lipid signaling (fatty acid derivatives)
  • protectins, maresins, and resolvins

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Published Papers (4 papers)

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Research

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17 pages, 1865 KiB  
Article
Severity-Dependent Long-Term Post-Traumatic Changes in the Circulating Oxylipin Profile
by Madlen Reinicke, Leyu Zheng, Moujie Rang, Carolin Fuchs, Juliane Weikert, Annette Keß, Christian Kleber, Uta Ceglarek, Georg Osterhoff and Gabriela Aust
Int. J. Mol. Sci. 2024, 25(24), 13530; https://doi.org/10.3390/ijms252413530 - 17 Dec 2024
Viewed by 945
Abstract
Trauma causes the breakdown of membrane phospholipids and the subsequent degradation of the released polyunsaturated fatty acids (PUFAs) to partially bioactive oxylipins. Here, we screened for circulating PUFAs and oxylipins in patients (n = 34) differing from those of uninjured controls (n = [...] Read more.
Trauma causes the breakdown of membrane phospholipids and the subsequent degradation of the released polyunsaturated fatty acids (PUFAs) to partially bioactive oxylipins. Here, we screened for circulating PUFAs and oxylipins in patients (n = 34) differing from those of uninjured controls (n = 25) and analyzed their diagnostic potential. Patients were followed up for 1 to 240 h after minor/moderate, severe, and very severe injuries. Of the targeted oxylipins, 13 out of 80 (13/80) were detected in almost all patients and controls. Injury caused a long-term decrease in 9- and 13-hydroxyoctadecadienoic acids and in several dihydroxyeicosatetraenoic acids, the stable derivatives of bioactive anti-inflammatory epoxyeicosatrienoic acids, compared to controls. Frequently, these oxylipins correlated inversely to injury severity, days in the intensive care unit and hospital, and/or procalcitonin and pro-inflammatory cytokine levels 48 up to 240 h after trauma. Notably, 20/80 oxylipins were detected in some patients but not or less often in controls. Many of these oxylipins increased transiently immediately after injury. Their level is partly correlated with adverse clinical parameters at this early time point. The circulating oxylipidome was markedly affected by trauma. Several oxylipins showed injury-dependent alterations at different time points in the post-traumatic course. Full article
(This article belongs to the Special Issue Advanced Research on Lipid Signaling Molecules)
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13 pages, 444 KiB  
Article
The Influence of an Anti-Inflammatory Gluten-Free Diet with EPA and DHA on the Involvement of Maresin and Resolvins in Hashimoto’s Disease
by Małgorzata Szczuko, Julia Kacprzak, Aleksandra Przybylska, Urszula Szczuko, Jakub Pobłocki, Anhelli Syrenicz and Arleta Drozd
Int. J. Mol. Sci. 2024, 25(21), 11692; https://doi.org/10.3390/ijms252111692 - 30 Oct 2024
Cited by 1 | Viewed by 2846
Abstract
The potential modulation of thyroid inflammatory conditions via a gluten-free diet has been suggested after establishing a link between Hashimoto’s thyroiditis (HT) and celiac disease. However, the majority of targeted studies in this field do not support the general recommendation of prescribing a [...] Read more.
The potential modulation of thyroid inflammatory conditions via a gluten-free diet has been suggested after establishing a link between Hashimoto’s thyroiditis (HT) and celiac disease. However, the majority of targeted studies in this field do not support the general recommendation of prescribing a gluten-free diet (GFD) for all HT patients. This study aims to analyze data regarding the impact of a GFD supplemented with eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), along with vegetables, on the course of inflammation involving long-chain fatty acid mediators. The study cohort consisted of 39 Caucasian female patients with autoimmune HT. Metabolite separations were performed using a liquid chromatograph with a DAD detector. Absorption peaks were read at 210 nm for resolvin E1, protectin DX, and maresin 1 and at 302 nm for resolvin D1. The introduction of a gluten-free diet completed with omega-3, including EPA and DHA, may contribute to a reduction in the inflammatory state in HT patients. This effect is supported by the elevation in the levels of anti-inflammatory mediators derived from long-chain fatty acids with anti-inflammatory properties but not by eliminating gluten. Significant statistical changes in the levels of all derivatives were observed before and after the implementation of the diet. It is worth noting that this effect was not observed in anti-TPO and anti-TG levels. The induction of anti-inflammatory changes can be achieved by supplementing the diet with EPA, DHA and vegetables with increased anti-inflammatory potential. Full article
(This article belongs to the Special Issue Advanced Research on Lipid Signaling Molecules)
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17 pages, 5343 KiB  
Article
Unveiling the Metabolomic Profile of Oily Sensitive Skin: A Non-Invasive Approach
by Jiaqi Zhang, Fan Wu, Jun Wang, Yi Qin and Yao Pan
Int. J. Mol. Sci. 2024, 25(20), 11033; https://doi.org/10.3390/ijms252011033 - 14 Oct 2024
Viewed by 1530
Abstract
Skin barrier impairment is becoming increasingly common due to changes in lifestyle and modern living environments. Oily sensitive skin (OSS) is a condition that is characterized by an impaired skin barrier. Thus, examining the differences between OSS and healthy skin will enable a [...] Read more.
Skin barrier impairment is becoming increasingly common due to changes in lifestyle and modern living environments. Oily sensitive skin (OSS) is a condition that is characterized by an impaired skin barrier. Thus, examining the differences between OSS and healthy skin will enable a more objective evaluation of the characteristics of OSS and facilitate investigations of potential treatments. Initially, a self-assessment questionnaire was used to identify patients with OSS. Biophysical measurements and LAST scores were used to determine whether skin barrier function was impaired. Epidermal biophysical properties, including skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), and a* value, were measured with noninvasive instruments. We subsequently devised a noninvasive D-square sampling technique to identify changes in the skin metabolome in conjunction with an untargeted metabolomics analysis with an Orbitrap Q ExactiveTM series mass spectrometer. In the stratum corneum of 47 subjects, 516 skin metabolites were identified. In subjects with OSS, there was an increase in the abundance of 15 metabolites and a decrease in the abundance of 48 metabolites. The participants with OSS were found to have the greatest disruptions in sphingolipid and amino acid metabolism. The results revealed that an impaired skin barrier is present in patients with OSS and offers a molecular target for screening for skin barrier damage. Full article
(This article belongs to the Special Issue Advanced Research on Lipid Signaling Molecules)
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Review

Jump to: Research

28 pages, 4240 KiB  
Review
Fluorescence-Based Enzyme Activity Assay: Ascertaining the Activity and Inhibition of Endocannabinoid Hydrolytic Enzymes
by Pierangela Ciuffreda, Ornella Xynomilakis, Silvana Casati and Roberta Ottria
Int. J. Mol. Sci. 2024, 25(14), 7693; https://doi.org/10.3390/ijms25147693 - 13 Jul 2024
Cited by 2 | Viewed by 2800
Abstract
The endocannabinoid system, known for its regulatory role in various physiological processes, relies on the activities of several hydrolytic enzymes, such as fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), monoacylglycerol lipase (MAGL), and α/β-hydrolase domains 6 (ABHD6) and 12 (ABHD12), [...] Read more.
The endocannabinoid system, known for its regulatory role in various physiological processes, relies on the activities of several hydrolytic enzymes, such as fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), monoacylglycerol lipase (MAGL), and α/β-hydrolase domains 6 (ABHD6) and 12 (ABHD12), to maintain homeostasis. Accurate measurement of these enzymes’ activities is crucial for understanding their function and for the development of potential therapeutic agents. Fluorometric assays, which offer high sensitivity, specificity, and real-time monitoring capabilities, have become essential tools in enzymatic studies. This review provides a comprehensive overview of the principles behind these assays, the various substrates and fluorophores used, and advances in assay techniques used not only for the determination of the kinetic mechanisms of enzyme reactions but also for setting up kinetic assays for the high-throughput screening of each critical enzyme involved in endocannabinoid degradation. Through this comprehensive review, we aim to highlight the strengths and limitations of current fluorometric assays and suggest future directions for improving the measurement of enzyme activity in the endocannabinoid system. Full article
(This article belongs to the Special Issue Advanced Research on Lipid Signaling Molecules)
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