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Bioactive Lipids: From the Perspective of Cellular and Molecular Mechanisms

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

Deadline for manuscript submissions: closed (30 May 2024) | Viewed by 8429

Special Issue Editors


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Guest Editor
National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041 Vladivostok, Russia
Interests: neurobiology of disease; neuropharmacology; neuroimmunology; glia

E-Mail Website
Guest Editor
The Pharmacology Laboratory of A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevskogo Str. 17, 690041 Vladivostok, Russia
Interests: neurobiology of disease; neuropharmacology; behavioral sciense

Special Issue Information

Dear Colleagues,

Lipids are a highly diverse group of bioorganic compounds and the main components of biological membranes. The most important biological properties of lipids are their influence on cell permeability and the activity of many enzymes, participation in the transmission of a nerve impulse, muscle contraction, the formation of intercellular contacts, and in immunochemical processes. The closest attention is paid to the study of polyunsaturated fatty acids (PUFAs), which, being structural components of phospholipids, affect the membranes’ permeability and fluidity, the activity of membrane-bound enzymes, and transport proteins. In addition, PUFAs are a substrate for the synthesis of pro- (eicosanoids, namely prostaglandins, prostacyclins, thromboxanes, and leukotrienes) and anti-inflammatory mediators (neuroprotectins, resolvins, maresins, fatty acid ethanolamides). The study of bioactive lipids activity, as well as changes in lipid metabolism in various disorders, will make it possible to understand precisely disease pathological aspects and find therapeutic targets. This special issue is aimed at revealing the cellular and molecular mechanisms of lipid participation in various pathological and physiological processes. The study of bioactive lipids opens up prospects for new drug development among lipid metabolism modulators. The search for natural lipid compounds can become a good source of potential therapeutic agents for the treatment or prevention of metabolic, inflammatory, and neurodegenerative diseases.

Dr. Igor Manzhulo
Dr. Anna A. Tyrtyshnaia
Guest Editors

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Keywords

  • lipids
  • polyunsaturated fatty acids
  • lipid metabolism
  • lipid mediators
  • inflammation
  • neuroprotection

Published Papers (6 papers)

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Research

30 pages, 10047 KiB  
Article
The Influence of Soy Isoflavones and Soy Isoflavones with Inulin on Kidney Morphology, Fatty Acids, and Associated Parameters in Rats with and without Induced Diabetes Type 2
by Kamila Misiakiewicz-Has, Dominika Maciejewska-Markiewicz, Dagmara Szypulska-Koziarska, Agnieszka Kolasa and Barbara Wiszniewska
Int. J. Mol. Sci. 2024, 25(10), 5418; https://doi.org/10.3390/ijms25105418 - 16 May 2024
Viewed by 513
Abstract
Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague–Dawley (SD) rats segregated into [...] Read more.
Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague–Dawley (SD) rats segregated into two cohorts: non-diabetic and diabetic, induced with type 2 diabetes (high-fat diet + two intraperitoneal streptozotocin injections). Each cohort was further divided into three subgroups (n = 6): control, isoflavone-treated, and isoflavone plus inulin-treated rats. Tail blood glucose and ketone levels were gauged. Upon termination, blood samples were drawn directly from the heart for urea, creatinine, and HbA1c/HbF analyses. One kidney per rat underwent histological (H-E) and immunohistochemical assessments (anti-AQP1, anti-AQP2, anti-AVPR2, anti-SLC22A2, anti-ACC-alpha, anti-SREBP-1). The remaining kidney underwent fatty acid methyl ester analysis. Results unveiled notable alterations in water intake, body and kidney mass, kidney morphology, fatty acids, AQP2, AVPR2, AcetylCoA, SREBP-1, blood urea, creatinine, and glucose levels in control rats with induced type 2 diabetes. Isoflavone supplementation exhibited favorable effects on plasma urea, plasma urea/creatinine ratio, glycemia, water intake, and kidney mass, morphology, and function in type 2 diabetic rats. Additional inulin supplementation frequently modulated the action of soy isoflavones. Full article
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10 pages, 865 KiB  
Article
The Specificities of Lysophosphatidic Acid Acyltransferase and Fatty Acid Desaturase Determine the High Content of Myristic and Myristoleic Acids in Cyanobacterium sp. IPPAS B-1200
by Alexander Y. Starikov, Roman A. Sidorov, Kirill S. Mironov and Dmitry A. Los
Int. J. Mol. Sci. 2024, 25(2), 774; https://doi.org/10.3390/ijms25020774 - 7 Jan 2024
Viewed by 896
Abstract
The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes [...] Read more.
The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes for lysophosphatidic acid acyltransferase (LPAAT; EC 2.3.1.51) and Δ9 fatty acid desaturase (FAD; EC 1.14.19.1) from Cyanobacterium sp. IPPAS B-1200 in Synechococcus elongatus PCC 7942, which synthesizes myristic and myristoleic acids at the level of 0.5–1% and produces mainly palmitic (~60%) and palmitoleic (35%) acids. S. elongatus cells that expressed foreign LPAAT synthesized myristic acid at 26%, but did not produce myristoleic acid, suggesting that Δ9-FAD of S. elongatus cannot desaturate FAs with chain lengths less than C16. Synechococcus cells that co-expressed LPAAT and Δ9-FAD of Cyanobacterium synthesized up to 45% palmitoleic and 9% myristoleic acid, suggesting that Δ9-FAD of Cyanobacterium is capable of desaturating saturated acyl chains of any length. Full article
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21 pages, 1644 KiB  
Article
Restorative Effect of Microalgae Nannochloropsis oceanica Lipid Extract on Phospholipid Metabolism in Keratinocytes Exposed to UVB Radiation
by Michał Biernacki, Tiago Conde, Anna Stasiewicz, Arkadiusz Surażyński, Maria Rosário Domingues, Pedro Domingues and Elżbieta Skrzydlewska
Int. J. Mol. Sci. 2023, 24(18), 14323; https://doi.org/10.3390/ijms241814323 - 20 Sep 2023
Cited by 1 | Viewed by 1060
Abstract
Ultraviolet B (UVB) radiation induces oxidative stress in skin cells, generating reactive oxygen species (ROS) and perturbing enzyme-mediated metabolism. This disruption is evidenced with elevated concentrations of metabolites that play important roles in the modulation of redox homeostasis and inflammatory responses. Thus, this [...] Read more.
Ultraviolet B (UVB) radiation induces oxidative stress in skin cells, generating reactive oxygen species (ROS) and perturbing enzyme-mediated metabolism. This disruption is evidenced with elevated concentrations of metabolites that play important roles in the modulation of redox homeostasis and inflammatory responses. Thus, this research sought to determine the impacts of the lipid extract derived from the Nannochloropsis oceanica microalgae on phospholipid metabolic processes in keratinocytes subjected to UVB exposure. UVB-irradiated keratinocytes were treated with the microalgae extract. Subsequently, analyses were performed on cell lysates to ascertain the levels of phospholipid/free fatty acids (GC-FID), lipid peroxidation byproducts (GC-MS), and endocannabinoids/eicosanoids (LC-MS), as well as to measure the enzymatic activities linked with phospholipid metabolism, receptor expression, and total antioxidant status (spectrophotometric methods). The extract from N. oceanica microalgae, by diminishing the activities of enzymes involved in the synthesis of endocannabinoids and eicosanoids (PLA2/COX1/2/LOX), augmented the concentrations of anti-inflammatory and antioxidant polyunsaturated fatty acids (PUFAs), namely DHA and EPA. These concentrations are typically diminished due to UVB irradiation. As a consequence, there was a marked reduction in the levels of pro-inflammatory arachidonic acid (AA) and associated pro-inflammatory eicosanoids and endocannabinoids, as well as the expression of CB1/TRPV1 receptors. The microalgal extract also mitigated the increase in lipid peroxidation byproducts, specifically MDA in non-irradiated samples and 10-F4t-NeuroP in both control and post-UVB exposure. These findings indicate that the lipid extract derived from N. oceanica, by mitigating the deleterious impacts of UVB radiation on keratinocyte phospholipids, assumed a pivotal role in reinstating intracellular metabolic equilibrium. Full article
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12 pages, 6226 KiB  
Article
Lipid Polyunsaturated Fatty Acid Chains in Mouse Kidneys Were Increased within 5 min of a Single High Dose Whole Body Irradiation
by Wenxin Li, Chi Zhang, Shuhei Aramaki, Lili Xu, Shogo Tsuge, Takumi Sakamoto, Md. Al Mamun, Ariful Islam, Takamitsu Hayakawa, Yusuke Takanashi, Maxime Dubail, Kenta Konishi, Tomohito Sato, Tomoaki Kahyo, Charles Fouillade, Katsumasa Nakamura and Mitsutoshi Setou
Int. J. Mol. Sci. 2023, 24(15), 12439; https://doi.org/10.3390/ijms241512439 - 4 Aug 2023
Cited by 2 | Viewed by 1244
Abstract
To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice’s kidneys, lungs, brains, and livers within 5 min of single [...] Read more.
To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice’s kidneys, lungs, brains, and livers within 5 min of single high-dose irradiation. In this study, we set up three groups of C56BL/6 male mice and conducted whole-body irradiation with 0 Gy, 10 Gy, and 20 Gy single doses. Kidney, lung, brain, and liver tissues were collected within 5 min of irradiation. PUFA-targeted and whole lipidomic analyses were conducted using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The results showed that PUFA chains of kidney phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG) significantly increased within 5 min of 10 Gy and 20 Gy irradiation. The main components of increased PUFA chains in PC and PE were C18:2, C20:4, and C22:6, and in TG the main component was C18:2. The kidney lipidomes also showed significant changes from the perspective of lipid species, mainly dominated by an increase in PC, PE, TG, and signal lipids, while lipidomes of the lung, brain, and liver were slightly changed. Our results revealed that acute PUFA chains increase and other lipidomic changes in the kidney upon whole-body irradiation within 5 min of irradiation. The significantly increased lipids also showed a consistent preference for possessing PUFA chains. The lipidomic changes varied from organ to organ, which indicates that the response upon irradiation within a short time is tissue-specific. Full article
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30 pages, 4866 KiB  
Article
Synaptamide Ameliorates Hippocampal Neurodegeneration and Glial Activation in Mice with Traumatic Brain Injury
by Anna Tyrtyshnaia, Olga Manzhulo and Igor Manzhulo
Int. J. Mol. Sci. 2023, 24(12), 10014; https://doi.org/10.3390/ijms241210014 - 11 Jun 2023
Viewed by 1325
Abstract
Traumatic brain injury (TBI) is a major concern for public health worldwide, affecting 55 million people and being the leading cause of death and disability. To improve the outcomes and effectiveness of treatment for these patients, we conducted a study on the potential [...] Read more.
Traumatic brain injury (TBI) is a major concern for public health worldwide, affecting 55 million people and being the leading cause of death and disability. To improve the outcomes and effectiveness of treatment for these patients, we conducted a study on the potential therapeutic use of N-docosahexaenoylethanolamine (synaptamide) in mice using the weight-drop injury (WDI) TBI model. Our study focused on exploring synaptamide’s effects on neurodegeneration processes and changes in neuronal and glial plasticity. Our findings showed that synaptamide could prevent TBI-associated working memory decline and neurodegenerative changes in the hippocampus, and it could alleviate decreased adult hippocampal neurogenesis. Furthermore, synaptamide regulated the production of astro- and microglial markers during TBI, promoting the anti-inflammatory transformation of the microglial phenotype. Additional effects of synaptamide in TBI include stimulating antioxidant and antiapoptotic defense, leading to the downregulation of the Bad pro-apoptotic marker. Our data suggest that synaptamide has promising potential as a therapeutic agent to prevent the long-term neurodegenerative consequences of TBI and improve the quality of life. Full article
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23 pages, 16845 KiB  
Article
Anti-Inflammatory Activity of Synaptamide in the Peripheral Nervous System in a Model of Sciatic Nerve Injury
by Anna Starinets, Anna Tyrtyshnaia and Igor Manzhulo
Int. J. Mol. Sci. 2023, 24(7), 6273; https://doi.org/10.3390/ijms24076273 - 27 Mar 2023
Cited by 5 | Viewed by 2370
Abstract
N-docosahexaenoylethanolamine (DHEA), or synaptamide, is an endogenous metabolite of docosahexaenoic acid (DHA) that exhibits synaptogenic and neurogenic effects. In our previous studies, synaptamide administration inhibited the neuropathic pain-like behavior and reduced inflammation in the central nervous system following sciatic nerve injury. In the [...] Read more.
N-docosahexaenoylethanolamine (DHEA), or synaptamide, is an endogenous metabolite of docosahexaenoic acid (DHA) that exhibits synaptogenic and neurogenic effects. In our previous studies, synaptamide administration inhibited the neuropathic pain-like behavior and reduced inflammation in the central nervous system following sciatic nerve injury. In the present study, we examine the effect of synaptamide on the peripheral nervous system in a neuropathic pain condition. The dynamics of ionized calcium-binding adapter molecule 1 (iba-1), CD68, CD163, myelin basic protein, and the production of interleukin 1β and 6 within the sciatic nerve, as well as the neuro-glial index and the activity of iba-1, CD163, glial fibrillary acidic protein (GFAP), neuronal NO synthase (nNOS), substance P (SP), activating transcription factor 3 (ATF3) in the dorsal root ganglia (DRG), are studied. According to our results, synaptamide treatment (4 mg/kg/day) (1) decreases the weight-bearing deficit after nerve trauma; (2) enhances the remyelination process in the sciatic nerve; (3) shows anti-inflammatory properties in the peripheral nervous system; (4) decreases the neuro-glial index and GFAP immunoreactivity in the DRG; (5) inhibits nNOS- and SP-ergic activity in the DRG, which might contribute to neuropathic pain attenuation. In general, the current study demonstrates the complex effect of synaptamide on nerve injury, which indicates its high potential for neuropathic pain management. Full article
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