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Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019
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Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019

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 (31 December 2019) | Viewed by 180005

Special Issue Editors

Dr. Gabriella Calviello

E-Mail Website
Guest Editor
Department of Translational Medicine and Surgery, Section of General Pathology, School of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito, 1-00168 Rome, Italy
Interests: cancer; nutrition; omega-3 fatty acids; antioxidants; phenolic compounds; inflammation; neurodegenerative diseases; metabolic diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Simona Serini

E-Mail Website
Guest Editor
Department of Translational Medicine and Surgery, Section of General Pathology, School of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito, 1-00168 Rome, Italy
Interests: cancer; nutrition; omega-3 fatty acids; antioxidants; phenolic compounds; inflammation; neurodegenerative diseases; nutrition; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past several decades, the beneficial properties of long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFA) have become extremely popular among the majority of the population. Usually, nutritionists recommend fish and nuts as dietary sources, and it has become a common practice to take ω-3 PUFA supplements for various accepted health reasons. On this basis, and in order to prevent them from becoming considered as a panacea on a non-scientific basis, there is an urgent need to gather recent scientific knowledge in the field, so as to precisely outline the current documented and specific ω-3 PUFA healthy properties as well as their possible harmful effects. This Special Issue intends to cover new advances in: (a) ω-3 PUFA effects and mechanisms of action in the areas of cardiovascular health, physiological development of the central nervous system, maintenance of cognitive functions, vision and mental health, as well as aging, immunity, inflammation, metabolism, epigenetics, and cancer; (b) the combination of ω-3 PUFA with other preventive or therapeutic agents; (c) genetic or metabolic conditions—and others—that could make individuals more/less sensitive to the effects of ω-3 PUFA; and (d) innovative ω-3 PUFA sources and delivery.

Prof. Dr. Gabriella Calviello
Dr. Simona Serini
Guest Editor

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Keywords

  • aging
  • cancer
  • cardiovascular diseases
  • delivery
  • inflammation
  • nanomaterials
  • neurologic disorders
  • omega-3 PUFA
  • personalized medicine
  • prevention and therapy

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Published Papers (19 papers)

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10 pages, 2024 KiB  
Article
Higher Accumulation of Docosahexaenoic Acid in the Vermilion of the Human Lip than in the Skin
by Md. Al Mamun, Shumpei Sato, Eiji Naru, Osamu Sakata, Emi Hoshikawa, Ayako Suzuki, Ariful Islam, Tomoaki Kahyo, Tomohito Sato, Takashi K. Ito, Makoto Horikawa, Reimu Fukui, Kenji Izumi and Mitsutoshi Setou
Int. J. Mol. Sci. 2020, 21(8), 2807; https://doi.org/10.3390/ijms21082807 - 17 Apr 2020
Cited by 12 | Viewed by 3961
Abstract
The vermilion of the human lip is a unique facial area because of certain distinguishing features from the adjacent tissues such as the white lip (skin) and oral mucosa. However, the distinction in terms of molecular distribution between the vermilion and skin has [...] Read more.
The vermilion of the human lip is a unique facial area because of certain distinguishing features from the adjacent tissues such as the white lip (skin) and oral mucosa. However, the distinction in terms of molecular distribution between the vermilion and skin has remained unexplored. Therefore, we aimed to map the human lip by mass spectrometry imaging to gain understanding of the free fatty acid distribution in the vermilion. The lip specimens trimmed off during cheiloplasty were analyzed using desorption electrospray ionization–mass spectrometry imaging. Distributions of two monounsaturated fatty acids and three polyunsaturated fatty acids were observed in the human lip tissue: palmitoleic acid (POA) and oleic acid (OA) and linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA), respectively. Although POA, OA, LA, and AA were differentially distributed across the vermilion and skin, DHA showed a higher accumulation in the epithelium of the vermilion compared to that in the skin. Our results clearly demonstrated the difference in fatty acid distributions between the vermilion and skin. The highly abundant DHA in the epithelium of the vermilion may have an antioxidant role and may thus protect the lip from aging. Our findings can provide a novel strategy for treating lip disorders. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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11 pages, 854 KiB  
Communication
Assessment of the Effect of Sorafenib on Omega-6 and Omega-3 Epoxyeicosanoid Formation in Patients with Hepatocellular Carcinoma
by Can G. Leineweber, Anne Pietzner, Ingrid W. Zhang, Usha B. Blessin, Michael Rothe, Eckart Schott, Nils H. Schebb and Karsten H. Weylandt
Int. J. Mol. Sci. 2020, 21(5), 1875; https://doi.org/10.3390/ijms21051875 - 9 Mar 2020
Cited by 20 | Viewed by 3494
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of epoxides derived from long-chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding diols. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) showed that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this pilot study, we assessed the effect of sorafenib treatment on the presence of lipid mediators, such as EETs, in blood of the patients with HCC using the lipidomics technology. We found a significant increase in 11,12-EET and 14,15-EET levels in HCC patients treated with sorafenib. Furthermore, while not significant in this small sample set, the data presented indicate that sorafenib can also increase the level of omega-3 DHA-derived 19,20-EDP. While the effect on EETs might hamper the anti-tumor effect of sorafenib, we hypothesize that supplementation of DHA in sorafenib-treated HCC patients could increase the level of 19,20-EDP and thereby enhance its anti-tumor effect. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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17 pages, 2343 KiB  
Article
EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression
by Zhilan Peng, Cai Zhang, Ling Yan, Yongping Zhang, Zhiyou Yang, Jiajia Wang and Cai Song
Int. J. Mol. Sci. 2020, 21(5), 1769; https://doi.org/10.3390/ijms21051769 - 5 Mar 2020
Cited by 104 | Viewed by 9884
Abstract
Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA [...] Read more.
Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1β were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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27 pages, 3609 KiB  
Article
Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice
by Debora Cutuli, Eugenia Landolfo, Davide Decandia, Annalisa Nobili, Maria Teresa Viscomi, Livia La Barbera, Stefano Sacchetti, Paola De Bartolo, Annacarmen Curci, Marcello D’Amelio, Stefano Farioli-Vecchioli and Laura Petrosini
Int. J. Mol. Sci. 2020, 21(5), 1741; https://doi.org/10.3390/ijms21051741 - 4 Mar 2020
Cited by 13 | Viewed by 5112 | Correction
Abstract
As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 [...] Read more.
As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 PUFA supplementation on behavioral deficits, hippocampal neurogenesis, volume loss, and astrogliosis in aged mice that underwent a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valid model to mimic a key component of the cognitive deficits associated with dementia. Aged mice were supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks and then cholinergically depleted with mu-p75-saporin immunotoxin. Two weeks after lesioning, mice were behaviorally tested to assess anxious, motivational, social, mnesic, and depressive-like behaviors. Subsequently, morphological and biochemical analyses were performed. In lesioned aged mice the n-3 PUFA pre-treatment preserved explorative skills and associative retention memory, enhanced neurogenesis in the dentate gyrus, and reduced volume and VAChT levels loss as well as astrogliosis in hippocampus. The present findings demonstrating that n-3 PUFA supplementation before cholinergic depletion can counteract behavioral deficits and hippocampal neurodegeneration in aged mice advance a low-cost, non-invasive preventive tool to enhance life quality during aging. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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13 pages, 2503 KiB  
Article
Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases
by Sébastien Gaertner, Cyril Auger, Muhammad A. Farooq, Brigitte Pollet, Sonia Khemais-Benkhiat, Zahid R. Niazi, Sophie Schrevens, Sin-Hee Park, Florence Toti, Dominique Stephan and Valérie B. Schini-Kerth
Int. J. Mol. Sci. 2020, 21(3), 920; https://doi.org/10.3390/ijms21030920 - 30 Jan 2020
Cited by 8 | Viewed by 2978
Abstract
In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins [...] Read more.
In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment—most likely via a cyclooxygenase-dependent mechanism. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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14 pages, 1818 KiB  
Article
Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease
by María Sánchez-Campillo, María José Ruiz-Pastor, Antonio Gázquez, Juan Marín-Muñoz, Fuensanta Noguera-Perea, Antonio J. Ruiz-Alcaraz, Salvadora Manzanares-Sánchez, Carmen Antúnez and Elvira Larqué
Int. J. Mol. Sci. 2020, 21(1), 70; https://doi.org/10.3390/ijms21010070 - 20 Dec 2019
Cited by 19 | Viewed by 4345
Abstract
The protein Major Facilitator Superfamily Domain containing 2A (MFSD2a) was recently described as the primary carrier for docosahexaenoic acid (DHA) into the brain. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by lower DHA levels in blood lipids. The aim of this [...] Read more.
The protein Major Facilitator Superfamily Domain containing 2A (MFSD2a) was recently described as the primary carrier for docosahexaenoic acid (DHA) into the brain. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by lower DHA levels in blood lipids. The aim of this study was to investigate the expression of MFSD2a in the whole blood and brain as a potential biomarker of AD. Three groups were established: 38 healthy controls, 48 subjects with moderate AD (GDS4), and 47 with severe AD (GDS6). We analyzed postmortem brain samples from the hippocampus of 11 healthy controls and 11 severe AD patients. Fatty acid (FA) was determined in serum and brain by gas chromatography. Blood and brain MFSD2a protein expression was analyzed by Western blotting. We found a significant and progressive decline of MFSD2a levels in blood of AD patients (Control 0.83 ± 0.13, GDS4 0.72 ± 0.09, GDS6 0.48 ± 0.05*, p ˂ 0.01). We also corroborated a significant reduction of DHA and other n-3 long-chain polyunsaturated FA in serum of AD. No differences were found in MFSD2a expression or FA levels in brain of controls and AD subjects. MFSD2A carrier was analyzed in AD patients for the first time and the level of MFSD2a in the whole blood could be a potential biomarker of this disease. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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18 pages, 3295 KiB  
Article
The Omega-3 Fatty Acids EPA and DHA, as a Part of a Murine High-Fat Diet, Reduced Lipid Accumulation in Brown and White Adipose Tissues
by Nikul Soni, Alastair B. Ross, Nathalie Scheers, Intawat Nookaew, Britt G. Gabrielsson and Ann-Sofie Sandberg
Int. J. Mol. Sci. 2019, 20(23), 5895; https://doi.org/10.3390/ijms20235895 - 24 Nov 2019
Cited by 35 | Viewed by 5893
Abstract
Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and [...] Read more.
Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are suggested to mitigate this inflammatory response, but the mechanisms are unclear, especially at the tissue level. Adipose tissues, the first tissues to give an inflammatory response, may be an important target site of action for EPA and DHA. To evaluate the effects of EPA and DHA in white and brown adipose tissues, we fed male C57Bl/6J mice either a high fat diet (HFD) with 5% corn oil, an HFD with 40% of the corn oil substituted for purified EPA and DHA triglycerides (HFD-ED), or normal chow, for 8 weeks. Fatty acid profiling and transcriptomics were used to study how EPA and DHA affect retroperitoneal white and brown adipose tissues. HFD-ED fed mice showed reduced lipid accumulation and levels of the pro-inflammatory fatty acid arachidonic acid in both white and brown adipose tissues, compared with HFD-corn oil fed animals. The transcriptomic analysis showed changes in β-oxidation pathways, supporting the decreased lipid accumulation in the HFD-ED fed mice. Therefore, our data suggests that EPA and DHA supplementation of a high fat diet may be anti-inflammatory, as well as reduce lipid accumulation in adipose tissues. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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11 pages, 2575 KiB  
Article
Endogenous n-3 Polyunsaturated Fatty Acids Are Beneficial to Dampen CD8+ T Cell-Mediated Inflammatory Response upon the Viral Infection in Mice
by Kyung Won Kang, Seyoung Kim, Yong-Bin Cho, Seung Rok Ryu, Young-Jin Seo and Sang-Myeong Lee
Int. J. Mol. Sci. 2019, 20(18), 4510; https://doi.org/10.3390/ijms20184510 - 12 Sep 2019
Cited by 14 | Viewed by 3503
Abstract
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) have been known to exert anti-inflammatory effects on various disease states. However, its effect on CD8+ T cell-mediated immunopathology upon viral infection has not been well elucidated yet. In this study, we investigated the [...] Read more.
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) have been known to exert anti-inflammatory effects on various disease states. However, its effect on CD8+ T cell-mediated immunopathology upon viral infection has not been well elucidated yet. In this study, we investigated the possible implication of n-3 PUFAs in CD8+ T cell responses against an acute viral infection. Infection of FAT-1 transgenic mice that are capable of synthesizing n-3 PUFAs from n-6 PUFAs with lymphocytic choriomeningitis virus (LCMV) resulted in significant reduction of anti-viral CD8+ T cell responses. Interestingly, expansion of adoptively transferred wild-type (WT) LCMV-specific T cell receptor (TCR) transgenic CD8+ (P14) T cells into FAT-1 mice was significantly decreased. Also, activation of anti-viral CD4+ helper T cells was reduced in FAT-1 mice. Importantly, P14 cells carrying the fat-1 gene that were adoptively transferred into WT mice exhibited a substantially decreased ability to proliferate and produce cytokines against LCMV infection. Together, n-3 PUFAs attenuated anti-viral CD8+ T cell responses against an acute viral infection and thus could be used to alleviate immunopathology mediated by the viral infection. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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19 pages, 4829 KiB  
Article
Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities
by Arzu Ulu, Prakash K. Sahoo, Ana G. Yuil-Valdes, Maheswari Mukherjee, Matthew Van Ormer, Philma Glora Muthuraj, Maranda Thompson, Ann Anderson Berry, Corrine K. Hanson, Sathish Kumar Natarajan and Tara M. Nordgren
Int. J. Mol. Sci. 2019, 20(18), 4402; https://doi.org/10.3390/ijms20184402 - 7 Sep 2019
Cited by 21 | Viewed by 5187
Abstract
Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory [...] Read more.
Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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12 pages, 2196 KiB  
Article
A Mixture of Polyunsaturated Fatty Acids ω-3 and ω-6 Reduces Melanoma Growth by Inhibiting Inflammatory Mediators in the Murine Tumor Microenvironment
by Ewin B. Almeida, Karina P.H. Silva, Vitoria Paixão, Jônatas B. do Amaral, Marcelo Rossi, Roberta A. Xavier-Navarro, Karina V. Barros, Vera L.F. Silveira, Rodolfo P. Vieira, Luis V.F. Oliveira, Elizabeth C. Perez, Miriam G. Jasiulionis and André L.L. Bachi
Int. J. Mol. Sci. 2019, 20(15), 3765; https://doi.org/10.3390/ijms20153765 - 1 Aug 2019
Cited by 12 | Viewed by 3601
Abstract
Background: Although it has been previously demonstrated that acute inflammation can promote the tumor growth of a sub-tumorigenic dose of melanoma cells through of 5-lipoxygenase inflammatory pathway and its product leukotriene B4, and also that the peritumoral treatment with eicosapentaenoic acid and [...] Read more.
Background: Although it has been previously demonstrated that acute inflammation can promote the tumor growth of a sub-tumorigenic dose of melanoma cells through of 5-lipoxygenase inflammatory pathway and its product leukotriene B4, and also that the peritumoral treatment with eicosapentaenoic acid and its product, leukotriene B5, reduces the tumor development, the effect of the treatment by gavage with omega-3 and omega-6 in the tumor microenvironment favorable to melanoma growth associated with acute inflammation has never been studied. Methods: C57BL/6 mice were coinjected with 1 × 106 apoptotic cells plus 1 × 103 viable melanoma cells into the subcutaneous tissue and treated by gavage with omega-3-rich fish oil or omega-6-rich soybean oil or a mixture of these oils (1:1 ratio) during five consecutive days. Results: The treatment by gavage with a mixture of fish and soybean oils (1:1 ratio) both reduced the melanoma growth and the levels of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), PGE2/prostaglandin E3 (PGE3) ratio, and CXC ligand 1 (CXCL1) and increased the levels of interleukin 10 (IL-10) to IL-10/CXCL1 ratio in the melanoma microenvironment. Conclusion: The oral administration of a 1:1 mixture of fish oil and soybean oil was able to alter the release of inflammatory mediators that are essential for a microenvironment favorable to the melanoma growth in mice, whereas fish oil or soybean oil alone was ineffective. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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13 pages, 1861 KiB  
Article
Comparison of the Substrate Preferences of ω3 Fatty Acid Desaturases for Long Chain Polyunsaturated Fatty Acids
by Pushkar Shrestha, Xue-Rong Zhou, Sapna Vibhakaran Pillai, James Petrie, Robert de Feyter and Surinder Singh
Int. J. Mol. Sci. 2019, 20(12), 3058; https://doi.org/10.3390/ijms20123058 - 22 Jun 2019
Cited by 6 | Viewed by 3183
Abstract
Omega-3 long chain polyunsaturated fatty acids (ω3 LC-PUFAs) such as eicosapentaenoic acid (EPA; 20:5ω3) and docosahexaenoic acid (DHA; 22:6ω3) are important fatty acids for human health. These ω3 LC-PUFAs are produced from their ω3 precursors by a set of desaturases and elongases involved [...] Read more.
Omega-3 long chain polyunsaturated fatty acids (ω3 LC-PUFAs) such as eicosapentaenoic acid (EPA; 20:5ω3) and docosahexaenoic acid (DHA; 22:6ω3) are important fatty acids for human health. These ω3 LC-PUFAs are produced from their ω3 precursors by a set of desaturases and elongases involved in the biosynthesis pathway and are also converted from ω6 LC-PUFA by omega-3 desaturases (ω3Ds). Here, we have investigated eight ω3-desaturases obtained from a cyanobacterium, plants, fungi and a lower animal species for their activities and compared their specificities for various C18, C20 and C22 ω6 PUFA substrates by transiently expressing them in Nicotiana benthamiana leaves. Our results showed hitherto unreported activity of many of the ω3Ds on ω6 LC-PUFA substrates leading to their conversion to ω3 LC-PUFAs. This discovery could be important in the engineering of EPA and DHA in heterologous hosts. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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11 pages, 1928 KiB  
Article
Elevated AA/EPA Ratio Represents an Inflammatory Biomarker in Tumor Tissue of Metastatic Colorectal Cancer Patients
by Valeria Tutino, Valentina De Nunzio, Maria Gabriella Caruso, Nicola Veronese, Dionigi Lorusso, Marta Di Masi, Maria Lucrezia Benedetto and Maria Notarnicola
Int. J. Mol. Sci. 2019, 20(8), 2050; https://doi.org/10.3390/ijms20082050 - 25 Apr 2019
Cited by 37 | Viewed by 6026
Abstract
Chronic inflammation increases the risk of developing certain types of cancer, such as colorectal cancer (CRC). The oxidative metabolism of polyunsaturated fatty acids (PUFAs) has a strong effect on colonic tumorigenesis and the levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA) can [...] Read more.
Chronic inflammation increases the risk of developing certain types of cancer, such as colorectal cancer (CRC). The oxidative metabolism of polyunsaturated fatty acids (PUFAs) has a strong effect on colonic tumorigenesis and the levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA) can contribute to the development of an inflammatory microenvironment. Aim of this study was to evaluate the possible differences in the AA/EPA ratio tissue levels between CRC patients with and without synchronous metastases. Moreover, the expression of the most important inflammatory enzymes and mediators, linked with the AA/EPA ratio, have been also assessed. Sixty-eight patients with CRC were enrolled in the study, of which 33 patients with synchronous metastasis. Fatty acid profile analysis in tissue samples was done to examine the levels of AA and EPA. High levels of the AA/EPA ratio were detected in tumor tissue of patients with metastatic CRC. Moreover, an increase of expression of the main enzymes and mediators involved in inflammation was also detected in the same samples. The lipidomic approach of inflammation allows to evaluate lipid homeostasis changes that occur in cancer and in its metastatic process, in order to identify new biomarkers to be introduced into clinical practice. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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Review

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26 pages, 966 KiB  
Review
Omega-3 Versus Omega-6 Polyunsaturated Fatty Acids in the Prevention and Treatment of Inflammatory Skin Diseases
by Anamaria Balić, Domagoj Vlašić, Kristina Žužul, Branka Marinović and Zrinka Bukvić Mokos
Int. J. Mol. Sci. 2020, 21(3), 741; https://doi.org/10.3390/ijms21030741 - 23 Jan 2020
Cited by 214 | Viewed by 37370
Abstract
Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in [...] Read more.
Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in cell membrane lipid composition, gene expression, cellular metabolism, and signal transduction. The application of ω-3 and ω-6 PUFAs in most common skin diseases has been examined in numerous studies, but their results and conclusions were mostly opposing and inconclusive. It seems that combined ω-6, gamma-linolenic acid (GLA), and ω-3 long-chain PUFAs supplementation exhibits the highest potential in diminishing inflammatory processes, which could be beneficial for the management of inflammatory skin diseases, such as atopic dermatitis, psoriasis, and acne. Due to significant population and individually-based genetic variations that impact PUFAs metabolism and associated metabolites, gene expression, and subsequent inflammatory responses, at this point, we could not recommend strict dietary and supplementation strategies for disease prevention and treatment that will be appropriate for all. Well-balanced nutrition and additional anti-inflammatory PUFA-based supplementation should be encouraged in a targeted manner for individuals in need to provide better management of skin diseases but, most importantly, to maintain and improve overall skin health. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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16 pages, 1304 KiB  
Review
Omega-3 Polyunsaturated Fatty Acids and Stroke Burden
by Yuji Ueno, Nobukazu Miyamoto, Kazuo Yamashiro, Ryota Tanaka and Nobutaka Hattori
Int. J. Mol. Sci. 2019, 20(22), 5549; https://doi.org/10.3390/ijms20225549 - 7 Nov 2019
Cited by 17 | Viewed by 6679
Abstract
Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet [...] Read more.
Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet is high in marine n-3 PUFAs, have a lower incidence of coronary heart disease than Western populations, numerous epidemiological studies to explore the associations of dietary intakes of fish and n-3 PUFAs with cardiovascular diseases, and large-scale clinical trials to identify the benefits of treatment with n-3 PUFAs have been conducted. In most of these studies the incidence and mortality of stroke were also evaluated mainly as secondary endpoints. Thus, a systematic literature review regarding the association of dietary intake of n-3 PUFAs with stroke in the epidemiological studies and the treatment effects of n-3 PUFAs in the clinical trials was conducted. Moreover, recent experimental studies were also reviewed to explore the molecular mechanisms of the neuroprotective effects of n-3 PUFAs after stroke. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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21 pages, 545 KiB  
Review
Effects of Omega-3 Fatty Acids on Immune Cells
by Saray Gutiérrez, Sara L Svahn and Maria E Johansson
Int. J. Mol. Sci. 2019, 20(20), 5028; https://doi.org/10.3390/ijms20205028 - 11 Oct 2019
Cited by 379 | Viewed by 40500
Abstract
Alterations on the immune system caused by omega-3 fatty acids have been described for 30 years. This family of polyunsaturated fatty acids exerts major alterations on the activation of cells from both the innate and the adaptive immune system, although the mechanisms for [...] Read more.
Alterations on the immune system caused by omega-3 fatty acids have been described for 30 years. This family of polyunsaturated fatty acids exerts major alterations on the activation of cells from both the innate and the adaptive immune system, although the mechanisms for such regulation are diverse. First, as a constitutive part of the cellular membrane, omega-3 fatty acids can regulate cellular membrane properties, such as membrane fluidity or complex assembly in lipid rafts. In recent years, however, a new role for omega-3 fatty acids and their derivatives as signaling molecules has emerged. In this review, we describe the latest findings describing the effects of omega-3 fatty acids on different cells from the immune system and their possible molecular mechanisms. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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22 pages, 1029 KiB  
Review
Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials
by Rossella Avallone, Giovanni Vitale and Marco Bertolotti
Int. J. Mol. Sci. 2019, 20(17), 4256; https://doi.org/10.3390/ijms20174256 - 30 Aug 2019
Cited by 134 | Viewed by 19136
Abstract
A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now [...] Read more.
A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represents a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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18 pages, 3837 KiB  
Review
Omega-3 Docosahexaenoic Acid Is a Mediator of Fate-Decision of Adult Neural Stem Cells
by Amanda Lo Van, Mayssa Hachem, Michel Lagarde and Nathalie Bernoud-Hubac
Int. J. Mol. Sci. 2019, 20(17), 4240; https://doi.org/10.3390/ijms20174240 - 30 Aug 2019
Cited by 13 | Viewed by 5990
Abstract
The mammalian brain is enriched with lipids that serve as energy catalyzers or secondary messengers of essential signaling pathways. Docosahexaenoic acid (DHA) is an omega-3 fatty acid synthesized de novo at low levels in humans, an endogenous supply from its precursors, and is [...] Read more.
The mammalian brain is enriched with lipids that serve as energy catalyzers or secondary messengers of essential signaling pathways. Docosahexaenoic acid (DHA) is an omega-3 fatty acid synthesized de novo at low levels in humans, an endogenous supply from its precursors, and is mainly incorporated from nutrition, an exogeneous supply. Decreased levels of DHA have been reported in the brains of patients with neurodegenerative diseases. Preventing this decrease or supplementing the brain with DHA has been considered as a therapy for the DHA brain deficiency that could be linked with neuronal death or neurodegeneration. The mammalian brain has, however, a mechanism of compensation for loss of neurons in the brain: neurogenesis, the birth of neurons from neural stem cells. In adulthood, neurogenesis is still present, although at a slower rate and with low efficiency, where most of the newly born neurons die. Neural stem/progenitor cells (NSPCs) have been shown to require lipids for proper metabolism for proliferation maintenance and neurogenesis induction. Recent studies have focused on the effects of these essential lipids on the neurobiology of NSPCs. This review aimed to introduce the possible use of DHA to impact NSPC fate-decision as a therapy for neurodegenerative diseases. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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19 pages, 666 KiB  
Review
Marine-Derived Omega-3 Polyunsaturated Fatty Acids and Heart Failure: Current Understanding for Basic to Clinical Relevance
by Atsushi Sakamoto, Masao Saotome, Keisuke Iguchi and Yuichiro Maekawa
Int. J. Mol. Sci. 2019, 20(16), 4025; https://doi.org/10.3390/ijms20164025 - 18 Aug 2019
Cited by 47 | Viewed by 10354
Abstract
Heart failure (HF) is a rapidly growing global public health problem. Since HF results in high mortality and re-hospitalization, new effective treatments are desired. Although it remains controversial, omega 3 polyunsaturated fatty acids (n-3 PUFAs), such as the eicosapentaenoic acid and docosahexaenoic acid, [...] Read more.
Heart failure (HF) is a rapidly growing global public health problem. Since HF results in high mortality and re-hospitalization, new effective treatments are desired. Although it remains controversial, omega 3 polyunsaturated fatty acids (n-3 PUFAs), such as the eicosapentaenoic acid and docosahexaenoic acid, have been widely recognized to have benefits for HF. In a large-scale clinical trial regarding secondary prevention of HF by n-3 PUFA (GISSI-HF trial), the supplementation of n-3 PUFA significantly reduced cardiovascular mortality and hospitalization. Other small clinical studies proposed that n-3 PUFA potentially suppresses the ventricular remodeling and myocardial fibrosis, which thereby improves the ventricular systolic and diastolic function both in ischemic and non-ischemic HF. Basic investigations have further supported our understanding regarding the cardioprotective mechanisms of n-3 PUFA against HF. In these reports, n-3 PUFA has protected hearts through (1) anti-inflammatory effects, (2) intervention of cardiac energy metabolism, (3) modification of cardiac ion channels, (4) improvement of vascular endothelial response, and (5) modulation of autonomic nervous system activity. To clarify the pros and cons of n-3 PUFA on HF, we summarized recent evidence regarding the beneficial effects of n-3 PUFA on HF both from the clinical and basic studies. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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Other

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1 pages, 180 KiB  
Correction
Correction: Cutuli et al. Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice. Int. J. Mol. Sci. 2020, 21, 1741
by Debora Cutuli, Eugenia Landolfo, Davide Decandia, Annalisa Nobili, Maria Teresa Viscomi, Livia La Barbera, Stefano Sacchetti, Paola De Bartolo, Annacarmen Curci, Marcello D’Amelio, Stefano Farioli-Vecchioli and Laura Petrosini
Int. J. Mol. Sci. 2022, 23(13), 6916; https://doi.org/10.3390/ijms23136916 - 22 Jun 2022
Viewed by 1283
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
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