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Polyunsaturated Fatty Acids: New Molecular Mechanisms and Nutritional Therapeutic Challenges

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Lipids".

Deadline for manuscript submissions: closed (25 May 2024) | Viewed by 11270

Special Issue Editors


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Guest Editor
1. Inserm Research Center UMR1231 "Lipids, Nutrition, Cancer", Université de Bourgogne, 7 Blvd Jeanne d’Arc, 21000 Dijon, France
2. Centre de Lutte Contre le Cancer Georges-François Leclerc Center, 21000 Dijon, France
Interests: polyhenols; flavonoids; degenerative age-related diseases; inflammation; cancers; chemosensitization; lipid metabolism
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Inserm Research Center UMR1231 "Lipids, Nutrition, Cancer", Université de Bourgogne, 7 Blvd Jeanne d’Arc, 21000 Dijon, France
Interests: lipid metabolism; cancers; chemoresistance; inflammation; bioactive molecules; degenerative diseases; age-related diseases

Special Issue Information

Dear Colleagues,

Among the molecules that have aroused great interest in the scientific community, polyunsaturated fatty acids (PUFAs) are of particular importance in terms of both nutrition and health. It has been clearly established that PUFAs, of natural or industrial origin, constitute aggravating or protective factors in various diseases (cardiovascular, cancer, inflammatory, etc.) and age-related processes. In this evolving scientific context, knowledge regarding the link between PUFAs and health is rapidly advancing. This Special Issue aims to cover areas related to the biosynthesis and distribution of PUFAs, their bioavailability and their health benefits, both in the field of nutritional prevention and in the therapeutic field. Specifically, this Special Issue will highlight newly discovered biological mechanisms of PUFAs and their derivatives in various pathologies, along with their potential applications. We invite authors to contribute original articles, as well as review articles, that provide the readers of Nutrients with novel and updated perspectives on PUFAs and their derivatives. We hope that this Special Issue will inspire new interest in the fields of preventive nutrition and therapeutic strategies for health.

Prof. Dr. Dominique Delmas
Dr. Virginie Aires
Guest Editors

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Keywords

  • polyunsaturated fatty acids
  • omega-3
  • nutrition
  • prevention
  • therapeutic strategies

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Published Papers (5 papers)

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Research

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19 pages, 4618 KiB  
Article
Dietary LPC-Bound n-3 LCPUFA Protects against Neonatal Brain Injury in Mice but Does Not Enhance Stem Cell Therapy
by Eva C. Hermans, Carlon C. E. van Gerven, Line Johnsen, Jørn E. Tungen, Cora H. Nijboer and Caroline G. M. de Theije
Nutrients 2024, 16(14), 2252; https://doi.org/10.3390/nu16142252 - 12 Jul 2024
Viewed by 995
Abstract
Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal [...] Read more.
Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21–28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy. Full article
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19 pages, 2826 KiB  
Article
Synbiotic Bacillus megaterium DSM 32963 and n-3 PUFA Salt Composition Elevates Pro-Resolving Lipid Mediator Levels in Healthy Subjects: A Randomized Controlled Study
by Bodo Speckmann, Tanja Wagner, Paul M. Jordan, Oliver Werz, Manfred Wilhelm, Heike tom Dieck and Christiane Schön
Nutrients 2024, 16(9), 1354; https://doi.org/10.3390/nu16091354 - 30 Apr 2024
Cited by 1 | Viewed by 1495
Abstract
Beneficial health effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n-3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory [...] Read more.
Beneficial health effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n-3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels. Healthy participants (n = 72) received either SynΩ3 (250 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) lysine salts; two billion CFU Bacillus megaterium; n = 23), placebo (n = 24), or fish oil (300 mg EPA plus DHA; N = 25) capsules daily for 28 days in a randomized, double-blind placebo-controlled parallel 3-group design. Biomarkers were assessed at baseline and after 2 and 28 days of intervention. The primary analysis involved the comparison between SynΩ3 and placebo. In addition, SynΩ3 was compared to fish oil. The synbiotic SynΩ3 comprising Bacillus megaterium DSM 32963 and n-3 PUFA salts significantly increased circulating SPM precursor levels, including 18-hydroxy-eicosapentaenoic acid (18-HEPE) plus 5-HEPE, which was not achieved to this extent by fish oil with a similar n-3 PUFA content. Omega-3 indices were increased slightly by both SynΩ3 and fish oil. These findings suggest reconsidering conventional n-3 PUFA supplementation and testing the effectiveness of SynΩ3 particularly in conditions related to inflammation. Full article
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22 pages, 13911 KiB  
Article
Low-Dose Dietary Fish Oil Improves RBC Deformability without Improving Post-Transfusion Recovery in Mice
by Christopher Y. Kim, Hannah J. Larsen, Steven L. Spitalnik, Eldad A. Hod, Richard O. Francis, Krystalyn E. Hudson, Dominique E. Gordy, Elizabeth F. Stone, Sandy Peltier, Pascal Amireault, Angelo D’Alessandro, James C. Zimring, Paul W. Buehler, Xiaoyun Fu and Tiffany Thomas
Nutrients 2023, 15(20), 4456; https://doi.org/10.3390/nu15204456 - 20 Oct 2023
Cited by 1 | Viewed by 1331
Abstract
Long-chain polyunsaturated fatty acids (LC-PUFAs) are important modulators of red blood cell (RBC) rheology. Dietary LC-PUFAs are readily incorporated into the RBC membrane, improving RBC deformability, fluidity, and hydration. Female C57BL/6J mice consumed diets containing increasing amounts of fish oil (FO) ad libitum [...] Read more.
Long-chain polyunsaturated fatty acids (LC-PUFAs) are important modulators of red blood cell (RBC) rheology. Dietary LC-PUFAs are readily incorporated into the RBC membrane, improving RBC deformability, fluidity, and hydration. Female C57BL/6J mice consumed diets containing increasing amounts of fish oil (FO) ad libitum for 8 weeks. RBC deformability, filterability, and post-transfusion recovery (PTR) were evaluated before and after cold storage. Lipidomics and lipid peroxidation markers were evaluated in fresh and stored RBCs. High-dose dietary FO (50%, 100%) was associated with a reduction in RBC quality (i.e., in vivo lifespan, deformability, lipid peroxidation) along with a reduced 24 h PTR after cold storage. Low-dose dietary FO (6.25–12.5%) improved the filterability of fresh RBCs and reduced the lipid peroxidation of cold-stored RBCs. Although low doses of FO improved RBC deformability and reduced oxidative stress, no improvement was observed for the PTR of stored RBCs. The improvement in RBC deformability observed with low-dose FO supplementation could potentially benefit endurance athletes and patients with conditions resulting from reduced perfusion, such as peripheral vascular disease. Full article
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20 pages, 4324 KiB  
Article
Linoleic Acid Induced Changes in SZ95 Sebocytes—Comparison with Palmitic Acid and Arachidonic Acid
by Dóra Kovács, Emanuela Camera, Szilárd Póliska, Alessia Cavallo, Miriam Maiellaro, Katalin Dull, Florian Gruber, Christos C. Zouboulis, Andrea Szegedi and Dániel Törőcsik
Nutrients 2023, 15(15), 3315; https://doi.org/10.3390/nu15153315 - 26 Jul 2023
Cited by 5 | Viewed by 2228
Abstract
Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid [...] Read more.
Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options. Full article
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Review

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19 pages, 1015 KiB  
Review
Variability in the Clinical Effects of the Omega-3 Polyunsaturated Fatty Acids DHA and EPA in Cardiovascular Disease—Possible Causes and Future Considerations
by Charalambos Michaeloudes, Stephanos Christodoulides, Panayiota Christodoulou, Theodora-Christina Kyriakou, Ioannis Patrikios and Anastasis Stephanou
Nutrients 2023, 15(22), 4830; https://doi.org/10.3390/nu15224830 - 18 Nov 2023
Cited by 5 | Viewed by 3560
Abstract
Cardiovascular disease (CVD) that includes myocardial infarction and stroke, is the leading cause of mortality worldwide. Atherosclerosis, the primary underlying cause of CVD, can be controlled by pharmacological and dietary interventions, including n-3 polyunsaturated fatty acid (PUFA) supplementation. n-3 PUFA supplementation, [...] Read more.
Cardiovascular disease (CVD) that includes myocardial infarction and stroke, is the leading cause of mortality worldwide. Atherosclerosis, the primary underlying cause of CVD, can be controlled by pharmacological and dietary interventions, including n-3 polyunsaturated fatty acid (PUFA) supplementation. n-3 PUFA supplementation, primarily consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has shown promise in reducing atherosclerosis by modulating risk factors, including triglyceride levels and vascular inflammation. n-3 PUFAs act by replacing pro-inflammatory fatty acid types in cell membranes and plasma lipids, by regulating transcription factor activity, and by inducing epigenetic changes. EPA and DHA regulate cellular function through shared and differential molecular mechanisms. Large clinical studies on n-3 PUFAs have reported conflicting findings, causing confusion among the public and health professionals. In this review, we discuss important factors leading to these inconsistencies, in the context of atherosclerosis, including clinical study design and the differential effects of EPA and DHA on cell function. We propose steps to improve clinical and basic experimental study design in order to improve supplement composition optimization. Finally, we propose that understanding the factors underlying the poor response to n-3 PUFAs, and the development of molecular biomarkers for predicting response may help towards a more personalized treatment. Full article
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