Nutrients

Research

15 pages, 3404 KiB

Open AccessArticle

n-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway

by Peiwen Zhang, Yuheng Pan, Shuang Wu, Yuxu He, Jinyong Wang, Lei Chen, Shunhua Zhang, Hui Zhang, Ye Zhao, Lili Niu, Mailin Gan, Yan Wang, Linyuan Shen and Li Zhu

Nutrients 2023, 15(8), 1927; https://doi.org/10.3390/nu15081927 - 16 Apr 2023

Cited by 3 | Viewed by 2105

Abstract

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by hyperandrogenemia with multiple suspended sinus follicles, thickened cortical tissue, and excessive proliferation of ovarian granulosa cells that severely affects the fertility and quality of life of women. The addition of n-3 PUFA [...] Read more.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by hyperandrogenemia with multiple suspended sinus follicles, thickened cortical tissue, and excessive proliferation of ovarian granulosa cells that severely affects the fertility and quality of life of women. The addition of n-3 PUFA to the diet may slightly reduce body weight and greatly alleviate disturbed blood hormone levels in PCOS mice. We treated KGN as a cell model for n-3 PUFA addition and showed that n-3 PUFA inhibited the proliferation of GCs and promoted ferroptosis in ovarian granulosa cells. We used CCK-8, fluorescence quantitative transmission electron microscopy experiments and ferroptosis marker gene detection and other methods. Furthermore, n-3 PUFA was found to promote YAP1 exocytosis by activating Hippo and weakening the cross-talk between YAP1 and Nrf2 by activating the Hippo signaling pathway. In this study, we found that n-3 PUFA inhibited the over proliferation of granulosa cells in ovarian follicles by activating Hippo, promoting YAP1 exocytosis, weakening the cross-talk between YAP1 and Nrf2, and ultimately activating the ferroptosis sensitivity of ovarian granulosa cells. We demonstrate that n-3 PUFA can alleviate the hormonal and estrous cycle disorder with PCOS by inhibiting the YAP1-Nrf2 crosstalk that suppresses over proliferating ovarian granulosa cells and promotes iron death in GCs. These findings reveal the molecular mechanisms by which n-3 PUFA attenuates PCOS and identify YAP1-Nrf2 as a potential therapeutic target for regulation granulosa cells in PCOS. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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10 pages, 713 KiB

Open AccessArticle

Increased Plasma L-Arginine Levels and L-Arginine/ADMA Ratios after Twelve Weeks of Omega-3 Fatty Acid Supplementation in Amateur Male Endurance Runners

by Zbigniew Jost, Maja Tomczyk, Maciej Chroboczek, Philip C. Calder, Helena L. Fisk, Katarzyna Przewłócka and Jędrzej Antosiewicz

Nutrients 2022, 14(22), 4749; https://doi.org/10.3390/nu14224749 - 10 Nov 2022

Viewed by 2924

Abstract

It is not fully understood how supplementation with omega-3 fatty acids affects the metabolism of amino acids required for the bioavailability/synthesis of NO, i.e., L-arginine (L-arg), asymmetric dimethylarginine (ADMA), their metabolites, and the L-arg/ADMA ratio and their impact on running economy (RE) in [...] Read more.

It is not fully understood how supplementation with omega-3 fatty acids affects the metabolism of amino acids required for the bioavailability/synthesis of NO, i.e., L-arginine (L-arg), asymmetric dimethylarginine (ADMA), their metabolites, and the L-arg/ADMA ratio and their impact on running economy (RE) in runners. Thus, 26 male amateur endurance runners completed a twelve-week study in which they were divided into two supplemented groups: the OMEGA group (n = 14; 2234 mg and 916 mg of eicosapentaenoic and docosahexaenoic acid daily) or the MCT group (n = 12; 4000 mg of medium-chain triglycerides daily). At the same time, all participants followed an endurance training program. Before and after the 12-week intervention, blood was collected from participants at two time points (at rest and immediately post-exercise) to determine EPA and DHA in red blood cells (RBCs) and plasma levels of L-arg, ADMA, and their metabolites. RBC EPA and DHA significantly increased in the OMEGA group (p < 0.001), which was related to the resting increase in L-arg (p = 0.001) and in the L-arg/ADMA ratio (p = 0.005) with no changes in the MCT group. No differences were found in post-exercise amino acid levels. A total of 12 weeks of omega-3 fatty acid supplementation at a dose of 2234 mg of EPA and 916 mg of DHA daily increased levels of L-arg and the L-arg/ADMA ratio, which indirectly indicates increased bioavailability/NO synthesis. However, these changes were not associated with improved RE in male amateur endurance runners. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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19 pages, 2114 KiB

Open AccessArticle

A Randomized Trial of the Effects of Dietary n3-PUFAs on Skeletal Muscle Function and Acute Exercise Response in Healthy Older Adults

by Hawley E. Kunz, Kelly L. Michie, Kevin J. Gries, Xiaoyan Zhang, Zachary C. Ryan and Ian R. Lanza

Nutrients 2022, 14(17), 3537; https://doi.org/10.3390/nu14173537 - 27 Aug 2022

Cited by 16 | Viewed by 5013

Abstract

Skeletal muscle is critical for maintaining mobility, independence, and metabolic health in older adults. However, a common feature of aging is the progressive loss of skeletal muscle mass and function, which is often accompanied by mitochondrial impairments, oxidative stress, and insulin resistance. Exercise [...] Read more.

Skeletal muscle is critical for maintaining mobility, independence, and metabolic health in older adults. However, a common feature of aging is the progressive loss of skeletal muscle mass and function, which is often accompanied by mitochondrial impairments, oxidative stress, and insulin resistance. Exercise improves muscle strength, mitochondrial health, and cardiorespiratory fitness, but older adults often exhibit attenuated anabolic responses to acute exercise. Chronic inflammation associated with aging may contribute to this “anabolic resistance” and therapeutic interventions that target inflammation may improve exercise responsiveness. To this end, we conducted a randomized controlled trial to determine the effect of 6 months of dietary omega-3 polyunsaturated fatty acids (n3-PUFA) supplementation on skeletal muscle function (mass, strength), mitochondrial physiology (respiration, ATP production, ROS generation), and acute exercise responsiveness at the level of the muscle (fractional synthesis rate) and the whole-body (amino acid kinetics) in healthy older adults. When compared with a corn oil placebo (n = 33; 71.5 ± 4.8 years), older adults treated with 4 g/day n3-PUFA (n = 30; 71.4 ± 4.5 years) exhibited modest but significant increases in muscle strength (3.1 ± 14.7% increase in placebo vs. 7.5 ± 14.1% increase in n3-PUFA; p = 0.039). These improvements in muscle strength with n3-PUFA supplementation occurred in the absence of any effects on mitochondrial function and a minor attenuation of the acute response to exercise compared to placebo. Together, these data suggest modest benefits of dietary n3-PUFAs to muscle function in healthy older adults. Future studies may elucidate whether n3-PUFA supplementation improves the exercise response in elderly individuals with co-morbidities, such as chronic inflammatory disease or sarcopenia. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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16 pages, 2336 KiB

Open AccessArticle

Synbiotic Compositions of Bacillus megaterium and Polyunsaturated Fatty Acid Salt Enable Self-Sufficient Production of Specialized Pro-Resolving Mediators

by Bodo Speckmann, Jessica Kleinbölting, Friedemann Börner, Paul M. Jordan, Oliver Werz, Stefan Pelzer, Heike tom Dieck, Tanja Wagner and Christiane Schön

Nutrients 2022, 14(11), 2265; https://doi.org/10.3390/nu14112265 - 28 May 2022

Cited by 1 | Viewed by 4144

Abstract

Specialized pro-resolving mediators (SPM) have emerged as crucial lipid mediators that confer the inflammation-resolving effects of omega-3 polyunsaturated fatty acids (n-3 PUFA). Importantly, SPM biosynthesis is dysfunctional in various conditions, which may explain the inconclusive efficacy data from n-3 PUFA [...] Read more.

Specialized pro-resolving mediators (SPM) have emerged as crucial lipid mediators that confer the inflammation-resolving effects of omega-3 polyunsaturated fatty acids (n-3 PUFA). Importantly, SPM biosynthesis is dysfunctional in various conditions, which may explain the inconclusive efficacy data from n-3 PUFA interventions. To overcome the limitations of conventional n-3 PUFA supplementation strategies, we devised a composition enabling the self-sufficient production of SPM in vivo. Bacillus megaterium strains were fed highly bioavailable n-3 PUFA, followed by metabololipidomics analysis and bioinformatic assessment of the microbial genomes. All 48 tested Bacillus megaterium strains fed with the n-3 PUFA formulation produced a broad range of SPM and precursors thereof in a strain-specific manner, which may be explained by the CYP102A1 gene polymorphisms that we detected. A pilot study was performed to test if a synbiotic Bacillus megaterium/n-3 PUFA formulation increases SPM levels in vivo. Supplementation with a synbiotic capsule product led to significantly increased plasma levels of hydroxy-eicosapentaenoic acids (5-HEPE, 15-HEPE, 18-HEPE) and hydroxy-docosahexaenoic acids (4-HDHA, 7-HDHA) as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in healthy humans. To the best of our knowledge, we report here for the first time the development and in vivo application of a self-sufficient SPM-producing formulation. Further investigations are warranted to confirm and expand these findings, which may create a new class of n-3 PUFA interventions targeting inflammation resolution. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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Review

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11 pages, 784 KiB

Open AccessReview

A Brief Narrative Review of the Underlying Mechanisms Whereby Omega-3 Fatty Acids May Influence Skeletal Muscle: From Cell Culture to Human Interventions

by Maryam Taheri, Philip D. Chilibeck and Stephen M. Cornish

Nutrients 2023, 15(13), 2926; https://doi.org/10.3390/nu15132926 - 28 Jun 2023

Cited by 4 | Viewed by 2642

Abstract

Skeletal muscle is essential for human locomotion as well as maintaining metabolic homeostasis. Age-related reduction in skeletal muscle mass, strength, and function (i.e., sarcopenia) is a result of pathophysiological processes that include inflammation, alteration of molecular signaling for muscle protein synthesis and degradation, [...] Read more.

Skeletal muscle is essential for human locomotion as well as maintaining metabolic homeostasis. Age-related reduction in skeletal muscle mass, strength, and function (i.e., sarcopenia) is a result of pathophysiological processes that include inflammation, alteration of molecular signaling for muscle protein synthesis and degradation, changes in insulin sensitivity, as well as altered skeletal muscle satellite cell activity. Finding strategies to mitigate skeletal muscle loss with age is deemed paramount as the percentage of the population continues to shift towards having more older adults with sarcopenia. Recent research indicates omega-3 fatty acid supplementation can influence anabolic or catabolic pathways in skeletal muscle. Our brief review will provide a synopsis of some underlying mechanisms that may be attributed to omega-3 fatty acid supplementation’s effects on skeletal muscle. We will approach this review by focusing on cell culture, animal (pre-clinical models), and human studies evaluating omega-3 fatty acid supplementation, with suggestions for future research. In older adults, omega-3 fatty acids may possess some potential to modify pathophysiological pathways associated with sarcopenia; however, it is highly likely that omega-3 fatty acids need to be combined with other anabolic interventions to effectively ameliorate sarcopenia. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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21 pages, 816 KiB

Open AccessReview

Effect of Omega-3 Fatty Acids on Telomeres—Are They the Elixir of Youth?

by Magdalena Ogłuszka, Paweł Lipiński and Rafał R. Starzyński

Nutrients 2022, 14(18), 3723; https://doi.org/10.3390/nu14183723 - 09 Sep 2022

Cited by 6 | Viewed by 6171

Abstract

Telomeres are complexes consisting of tandem repeat DNA combined with associated proteins that play a key role in protecting the ends of chromosomes and maintaining genome stability. They are considered a biological clock, as they shorten in parallel with aging. Furthermore, short telomeres [...] Read more.

Telomeres are complexes consisting of tandem repeat DNA combined with associated proteins that play a key role in protecting the ends of chromosomes and maintaining genome stability. They are considered a biological clock, as they shorten in parallel with aging. Furthermore, short telomeres are associated with several age-related diseases. However, the variability in telomere shortening independent of chronological age suggests that it is a modifiable factor. In fact, it is regulated inter alia by genetic damage, cell division, aging, oxidative stress, and inflammation. A key question remains: how can we prevent accelerated telomere attrition and subsequent premature replicative senescence? A number of studies have explored the possible impact of omega-3 fatty acids on telomere shortening. This review summarizes published cross-sectional studies, randomized controlled trials, and rodent studies investigating the role of omega-3 fatty acids in telomere biology. It also covers a broad overview of the mechanism, currently favored in the field, that explains the impact of omega-3 fatty acids on telomeres—the food compound’s ability to modulate oxidative stress and inflammation. Although the results of the studies performed to date are not consistent, the vast majority indicate a beneficial effect of omega-3 fatty acids on telomere length. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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12 pages, 273 KiB

Open AccessReview

Omega-3 Fatty Acids for the Management of Osteoarthritis: A Narrative Review

by Dean M. Cordingley and Stephen M. Cornish

Nutrients 2022, 14(16), 3362; https://doi.org/10.3390/nu14163362 - 16 Aug 2022

Cited by 7 | Viewed by 4575

Abstract

Osteoarthritis (OA) is a disease which results in degeneration of cartilage within joints and affects approximately 13.6% of adults over 20 years of age in Canada and the United States of America. OA is characterized by a state of low-grade inflammation which leads [...] Read more.

Osteoarthritis (OA) is a disease which results in degeneration of cartilage within joints and affects approximately 13.6% of adults over 20 years of age in Canada and the United States of America. OA is characterized by a state of low-grade inflammation which leads to a greater state of cellular catabolism disrupting the homeostasis of cartilage synthesis and degradation. Omega-3 polyunsaturated fatty acids (PUFAs) have been postulated as a potential therapeutic treatment option for individuals with OA. Omega-3 PUFAs are recognized for their anti-inflammatory properties, which could be beneficial in the context of OA to moderate pro-inflammatory markers and cartilage loss. The purpose of this narrative review is to outline recent pre-clinical and clinical evidence for the use of omega-3 in the management of OA. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

29 pages, 2251 KiB

Open AccessEditor’s ChoiceReview

Poultry Meat and Eggs as an Alternative Source of n-3 Long-Chain Polyunsaturated Fatty Acids for Human Nutrition

by Alice Cartoni Mancinelli, Simona Mattioli, Cornelia Twining, Alessandro Dal Bosco, Ann M. Donoghue, Komala Arsi, Elisa Angelucci, Diletta Chiattelli and Cesare Castellini

Nutrients 2022, 14(9), 1969; https://doi.org/10.3390/nu14091969 - 08 May 2022

Cited by 32 | Viewed by 4361

Abstract

The beneficial effects of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on human health are widely known. Humans are rather inefficient in synthesizing n-3 LC-PUFA; thus, these compounds should be supplemented in the diet. However, most Western human diets have unbalanced n-6/n-3 ratios [...] Read more.

The beneficial effects of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on human health are widely known. Humans are rather inefficient in synthesizing n-3 LC-PUFA; thus, these compounds should be supplemented in the diet. However, most Western human diets have unbalanced n-6/n-3 ratios resulting from eating habits and the fact that fish sources (rich in n-3 LC-PUFA) are not sufficient (worldwide deficit ~347,956 t/y) to meet the world requirements. In this context, it is necessary to find new and sustainable sources of n-3 LC-PUFA. Poultry products can provide humans n-3 LC-PUFA due to physiological characteristics and the wide consumption of meat and eggs. The present work aims to provide a general overview of the main strategies that should be adopted during rearing and postproduction to enrich and preserve n-3 LC-PUFA in poultry products. The strategies include dietary supplementation of α-Linolenic acid (ALA) or n-3 LC-PUFA, or enhancing n-3 LC-PUFA by improving the LA (Linoleic acid)/ALA ratio and antioxidant concentrations. Moreover, factors such as genotype, rearing system, transport, and cooking processes can impact the n-3 LC-PUFA in poultry products. The use of a multifactorial view in the entire production chain allows the relevant enrichment and preservation of n-3 LC-PUFA in poultry products. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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Other

Jump to: Research, Review

9 pages, 2064 KiB

Open AccessBrief Report

Palatability and Acceptability of Flaxseed-Supplemented Foods in Children with Sickle Cell Disease

by Chinenye R. Dike, Jeffrey Lebensburger, Ciara Mitchell, Betty Darnell, Casey D. Morrow and Wendy Demark-Wahnefried

Nutrients 2023, 15(5), 1245; https://doi.org/10.3390/nu15051245 - 01 Mar 2023

Cited by 1 | Viewed by 1544

Abstract

Omega-3 fatty acids (w3FAs) have demonstrated benefits in several inflammatory disease states; however, limited research has been conducted in sickle cell disease (SCD). While marine-based w3FAs are used, their strong odor and taste are a barrier to long-term use. Plant-based sources, especially those [...] Read more.

Omega-3 fatty acids (w3FAs) have demonstrated benefits in several inflammatory disease states; however, limited research has been conducted in sickle cell disease (SCD). While marine-based w3FAs are used, their strong odor and taste are a barrier to long-term use. Plant-based sources, especially those in whole foods, may circumvent this barrier. We tested whether flaxseed (rich source of w3FAs) was acceptable to children with SCD. A cross-sectional tasting trial of flaxseed added to baked products (cookies, pancakes, brownies) or to readily available foods (applesauce, pudding, yogurt) was conducted among 30 children (median age = 13 years) reporting to a clinic for routine follow-up, sick visits, or transfusion for SCD to determine acceptability. A food preference rank scale (1–7) was used to rank products based on taste, sight, smell, and texture. An average score for each product was computed. Children were also asked to rank their top three products. The top-ranked products were flaxseed baked in brownies and cookies and ground flaxseed added to yogurt. More than 80% of participants indicated willingness to be contacted for a follow-up study in which a flaxseed-supplemented diet would be evaluated for mitigation of SCD-associated pain. In conclusion, flaxseed-enriched products are palatable and acceptable in children with SCD. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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16 pages, 1284 KiB

Open AccessSystematic Review

The Effects of Omega-3 Supplementation on Depression in Adults with Cardiometabolic Disease: A Systematic Review of Randomised Control Trials

by Franciskos Arsenyadis, Ehtasham Ahmad, Emma Redman, Thomas Yates, Melanie Davies and Kamlesh Khunti

Nutrients 2022, 14(9), 1827; https://doi.org/10.3390/nu14091827 - 27 Apr 2022

Cited by 2 | Viewed by 3179

Abstract

Background: Omega-3 polyunsaturated fatty acids′ concurrent benefits for cardiometabolic and mental health are equivocal. Despite lack of evidence, up to a third of adults consume Omega-3 supplements. No review has yet been published to report effect on depression in this cardiometabolic population. Methods: [...] Read more.

Background: Omega-3 polyunsaturated fatty acids′ concurrent benefits for cardiometabolic and mental health are equivocal. Despite lack of evidence, up to a third of adults consume Omega-3 supplements. No review has yet been published to report effect on depression in this cardiometabolic population. Methods: We conducted a systematic review of double-blinded, controlled randomised trials to investigate the safety and effect of Omega-3 supplementation on depression scores in people with cardiometabolic diseases. Primary outcome was change in depression scores versus placebo. Secondary outcomes were side-effects, concurrent medication and adherence. Results: Seven trials reporting on 2575 (672 female) adults aged 39–73 were included. Omega-3 dosages ranged from 1–3 g with an intervention duration of 10–48 weeks. Six out of seven trials found no statistically or clinically significant change to depression scores compared to placebo. One trial favoured intervention (Relative Risk Reduction: 47.93%, 95% CI: 24.89–63.98%, p < 0.001). Sub-analyses showed clinically meaningful reductions in depression scores for those on antidepressants (Intervention: 20.9 (SD: 7.1), Placebo: 24.9 (SD: 8.5) p < 0.05) or with severe depression (−1.74; 95% CI −3.04 to −0.05, p < 0.05) in two separate trials. Side effects were comparable between treatment arms. Conclusions: Omega-3 supplementation is safe to use but not superior to placebo for depression in adults with concurrent cardiometabolic disease. Full article

(This article belongs to the Special Issue Dietary Supplementation with Omega-3 Fatty Acids in Health and Disease)

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