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Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.

Maternal diet influences breast milk nutritional profile; however, it is unclear which nutrients and contaminants are particularly responsive to short- and long-term changes in maternal intake, and the impact of specific exclusion diets, such as vegan or vegetarian. This study systematically reviewed the literature on the effects of maternal nutrient intake, including exclusion diets, on both the nutrient and contaminant content of breast milk. The electronic databases, PubMed, CENTRAL, Web of Science and CINALH were systematically searched until 4 June 2023, with additionally searches of reference lists (PROSPERO, CRD42020221577). The quality of the studies was examined using Cochrane Risk of Bias tool and Newcastle–Ottawa scale. Eighty-eight studies (n 6577) met the search criteria. Due to high heterogeneity, meta-analysis was not possible. There was strong evidence of response to maternal intakes for DHA and EPA, vitamins A, E and K, iodine and Se in breast milk composition, some evidence of response for α -linolenic acid, B vitamins, vitamin C and D, ovalbumin, tyrosine and contaminants, and insufficient evidence to identify the effects arachidonic acid, Cu, Fe, Zn and choline. The paucity of evidence and high heterogeneity among studies reflects the need for more high-quality trials. However, this review identified the importance of maternal intake in the nutritional content of breast milk for a wide range of nutrients and supports the recommendation for supplementation of DHA and vitamin B12 for those on restrictive diets. [ABSTRACT FROM AUTHOR]

Neurogenesis occurs in limited areas of the adult mammalian brain, and has been reported in the hippocampus of rodents and man. Neurogenesis is enhanced in conditions associated with enhanced synaptic plasticity and following neuronal injury, suggesting a role for neurogenesis in cognition and brain repair. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to promote hippocampal neurogenesis in a variety of models. Importantly, recent work has shown that the fat-1 transgenic mouse, an animal model of endogenous omega-3 PUFA enrichment, exhibits enhanced neurogenesis, with concomitant improvements in spatial memory compared to wild type mice. During ageing, the rate of neurogenesis declines significantly and there is a strong correlation between memory impairment in hippocampal-dependent tasks and this decline. Interestingly, there is a strong correlation between omega-3 PUFA and hippocampal-dependent memory tasks, and we have recently shown that supplementation of aged rats with omega-3 PUFAs partially reverses the age-related decline in neurogenesis. Thus omega-3 PUFAs positively influence neurogenesis, and these effects may contribute to improved cognitive performance. However, the mechanisms by which omega-3 PUFAs regulate neurogenesis remain unclear, although a number or putative targets have been suggested. The aims of this paper are to review the role of omega-3 PUFA in hippocampal neurogenesis, and explore some of the potential mechanisms of action which may underlie the observed effects.

This document is a correction notice for an article titled "The Omega-3 Fatty Acid Eicosapentaenoic Acid Accelerates Disease Progression in a Model of Amyotrophic Lateral Sclerosis." The correction states that there are errors in the numerical values presented in Table 1 and provides the correct table. The table shows that mice administered with either a single bolus dose of EPA or fed with an EPA enriched diet had higher levels of EPA and DHA in their plasma compared to mice fed on the control diet. The correction also mentions an error in the second sentence of the first paragraph of the "Increased plasma EPA content after oral gavage or dietary supplementation with EPA" subsection of the Results, providing the correct sentence. The authors of the article are listed as Ping K. Yip, Chiara Pizzasegola, Stacy Gladman, Maria Luigia Biggio, Marianna Marino, Maduka Jayasinghe, Farhan Ullah, Simon C. Dyall, Andrea Malaspina, Caterina Bendotti, and Adina Michael-Titus. [Extracted from the article]

There is now evidence to suggest that there may be an interaction between B vitamins and n -3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n -3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n -3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n -3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n -3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60–70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n -3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n -3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work. [ABSTRACT FROM AUTHOR]

The article focuses on assessment of neoroprotective and proregenerative potential of omega-3 polyunsaturated fatty acids (PUFA) in peripheral nerve injury (PNI) in mice that express the fat-1 gene encoding for omega-3 fatty acid desaturase that increases endogenous omega-3 PUFAs and a concomitant decrease in omega-6 PUFAs. It concludes through in vitro and in vivo experiments that a higher endogenous omega-3 PUFA could have beneficial effects after a PNI.

Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Evidence suggests that polyunsaturated fatty acids (PUFAs) could target some of the pathological mechanisms that underlie damage after SCI. We examined the effects of treatment with PUFAs after lateral spinal cord hemisection in the rat. The ω-3 PUFAs α-linolenic acid and docosahexaenoic acid (DHA) injected 30 min after injury induced significantly improved locomotor performance and neuroprotection, including decreased lesion size and apoptosis and increased neuronal and oligodendrocyte survival. Evidence showing a decrease in RNA/DNA oxidation suggests that the neuroprotective effect of ω-3 PUFAs involved a significant antioxidant function. In contrast, animals treated with arachidonic acid, an ω-6 PUFA, had a significantly worse outcome than controls. We confirmed the neuroprotective effect of ω-3 PUFAs by examining the effects of DHA treatment after spinal cord compression injury. Results indicated that DHA administered 30 min after spinal cord compression not only greatly increased survival of neurons but also resulted in significantly better locomotor performance for up to 6 weeks after injury. This report shows a striking difference in efficacy between the effects of treatment with ω-3 and ω-6 PUFAs on the outcome of SCI, with ω-3 PUFAs being neuroprotective and ω-6 PUFAs having a damaging effect. Given the proven clinical safety of ω-3 PUFAs, our observations show that these PUFAs have significant therapeutic potential in SCI. In contrast, the use of preparations enriched in ω-6 PUFAs after injury could worsen outcome after SCI. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) leads to major membrane lipid breakdown. We investigated plasma lipids over 3 days post-TBI, to identify a signature of acute human TBI and assess its correlation with neuronal injury and inflammation. Plasma from patients with TBI (Abbreviated Injury Scale (AIS)3 - serious injury, n = 5; AIS4 - severe injury, n = 8), and controls (n = 13) was analysed for lipidomic profile, neurofilament light (NFL) and cytokines, and the omega-3 index was measured in red blood cells. A lipid signature separated TBI from controls, at 24 and 72 h. Major species driving the separation were: lysophosphatidylcholine (LPC), phosphatidylcholine (PC) and hexosylceramide (HexCer). Docosahexaenoic acid (DHA, 22:6) and LPC (0:0/22:6) decreased post-injury. NFL levels were increased at 24 and 72 h post-injury in AIS4 TBI vs. controls. Interleukin (IL-)6, IL-2 and IL-13 were elevated at 24 h in AIS4 patients vs. controls. NFL and IL-6 were negatively correlated with several lipids. The omega-3 index at admission was low in all patients (controls: 4.3 ± 1.1% and TBI: 4.0 ± 1.1%) and did not change significantly over 3 days post-injury. We have identified specific lipid changes, correlated with markers of injury and inflammation in acute TBI. These observations could inform future lipid-based therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Donor human milk (DHM) is used as alternative to maternal milk to feed preterm infants; however, it may provide less long-chain (LC) polyunsaturated fatty acids (PUFAs) and more oxidized lipids, which may be detrimental to preterm infant health and development. Levels have not been reported for DHM in the United Kingdom., Methods: DHM (n = 19) from 2 neonatal units, preterm milk from a neonatal unit (n = 10), and term milk from the community (n = 11) were analyzed for fatty acids, malondialdehyde, 4-hydroxy-2-nonenal, and hexanal., Study Registration: NCT03573531., Results: DHM had significantly lower absolute LCPUFA content than term (P < .001) and significantly lower ω-3 PUFAs than preterm milk (P < .05), although relative LCPUFA composition did not differ. Exclusive DHM feeding leads to significantly lower fat (3.7 vs 6.7 g/d) and LCPUFA (docosahexaenoic acid [DHA]: 10.6 vs 16.8 mg/d; arachidonic acid [ARA]: 17.4 vs 25.2 mg/d) intake than recommended by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, and provides 17.3% and 43.1% of the in utero accreted ARA and DHA. DHM had the highest proportion of lipid peroxidation., Conclusions: This study confirms that DHM in the United Kingdom has insufficient LCPUFAs for preterm infants. It demonstrates for the first time that DHM has the highest level of lipid peroxidation, compared with preterm or term milk. This has important implications for preterm infant nutrition, as exclusive DHM feeding might not be suitable long term and may contribute to the development of major preterm neonatal morbidities., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Functional recovery after a peripheral nerve injury (PNI) is often poor. There is a need for therapies that protect neurons against injury and enhance regeneration. ω-3 polyunsaturated fatty acids (PUFAs) have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury. The objective of this study was to assess the neuroprotective and pro-regenerative potential of ω-3 PUFAs in PNI. We investigated this in mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs. Dorsal root ganglion (DRG) neurons from wild-type or fat-1 mice were subjected to a mechanical strain or hypoxic injury, and cell death was assessed using ethidium homodimer-1 labeling. The fat-1 background appears to confer robust neuroprotection against both injuries. We then examined the early functional and morphological changes in wild-type and fat-1 mice after a sciatic nerve crush. An accelerated functional recovery 7 d after injury was seen in fat-1 mice when assessed using von Frey filaments and the sciatic nerve functional index. These observations were also mapped to changes in injury-related markers. The injury-induced expression of ATF-3 was decreased in the DRG of fat-1 mice, whereas the axons detected 6 mm distal to the crush were increased. Fat-1 animals also had some protection against muscle atrophy after injury. In conclusion, both in vitro and in vivo experiments support the idea that a higher endogenous ω-3 PUFA could lead to beneficial effects after a PNI.