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Update on Fatty Acids and the Brain

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

Deadline for manuscript submissions: closed (5 May 2024) | Viewed by 32120

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Dr. Andrew J. Sinclair

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Department of Nutrition, Dietetics, and Food, Monash University, Melbourne, VIC, Australia
Interests: nutritional biochemistry and food science;n-3 DPA; krill oil; DHA; postprandial studies; bioavailability
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Special Issue Information

Dear colleagues,

It has been known for more than a century that the brain is rich in lipids representing 50-60% of the dry weight. Lipids play a fundamental role in the critical structural development of the brain, with an uneven distribution throughout the brain regions and cells contributing to dynamic nanodomains. Lipid categories found in the brain include fatty acyls, endocannabinoids, glycerolipids, glycerophospholipids, sphingolipids, sterols, prenol lipids, and saccharolipids. Amongst these, their fatty acid components, which are often unique in neuronal membranes, deserve mentioning, including phosphatidylserines rich in docosahexaenoic acid (DHA); sphingomyelin, cerebrosides, sulfatides, and gangliosides rich in long-chain saturated and hydroxy-fatty acids; and glycerophospholipids rich in DHA, arachidonic acid, and docosatetraenoic acid. These lipids and their fatty acids contribute to many aspects of brain function and development, having major roles in membrane structure (order), in membrane receptor function, and as precursors of specialised lipid mediators. Recent developments in analysis has enhanced the progress in understanding the localisation of more than 10,000 lipid molecular species. There is still much multi-disciplinary work required to unravel the roles of these important biological molecules in areas such as brain development, mood disorders, and the ageing brain.

This Special Issue encourages the submission of original research articles on methodological developments, meta-analyses, and reviews of scientific literature relevant to human health and disease.

Dr. Andrew J. Sinclair
Guest Editor

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Keywords

ageing
Alzheimer’s disease
arachidonic acid
brain-derived neurotrophic factor
brain development
cognition
Delta-6 KO
depression
docosahexaenoic acid
docosatetraenoic acid
docosapentaenoic acid (n-3)
eicosapentaenoic acid
hydroxy fatty acids
inflammation
lipidomics
mood
myelin
oxidative changes
plasmalogens
phosphatidyl serine
saturated fatty acids
specialised lipid mediators
traumatic brain injury

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Published Papers (9 papers)

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Research

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20 pages, 2216 KiB

Open AccessArticle

Effects of Long-Chain Polyunsaturated Fatty Acids in Combination with Lutein and Zeaxanthin on Episodic Memory in Healthy Older Adults

by Toshiaki Sueyasu, Keisuke Yasumoto, Hisanori Tokuda, Yoshihisa Kaneda, Hidenori Obata, Tomohiro Rogi, Takayuki Izumo, Sumio Kondo, Jiro Saito, Takashi Tsukiura and Masaaki Nakai

Nutrients 2023, 15(13), 2825; https://doi.org/10.3390/nu15132825 - 21 Jun 2023

Cited by 6 | Viewed by 3570

Abstract

Arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), which are long-chain polyunsaturated fatty acids (LCPUFAs), as well as lutein (L) and zeaxanthin (Z), can potentially improve brain function. However, the effect of a combination of these components (LCPUFAs + LZ) on memory function in healthy older individuals remains unclear. This study aimed to determine if LCPUFAs + LZ-supplemented food could improve memory function. Exploratory and confirmatory trials (Trials 1 and 2, respectively) were conducted in healthy older Japanese individuals with memory complaints. We conducted randomized, double-blind, placebo-controlled, parallel-group trials. Participants were randomly allocated to two groups: placebo or LCPUFAs + LZ. LCPUFAs + LZ participants were provided with supplements containing ARA, DHA, EPA, L, and Z for 24 weeks in Trial 1 and 12 weeks in Trial 2. Memory functions were evaluated using Cognitrax before and after each trial. Combined analyses were performed for subgroups of participants with cognitive decline in Trials 1 and 2. The results showed that supplementation with LCPUFAs + LZ did not significantly affect memory function in healthy, non-demented, older individuals with memory complaints whereas it improved memory function in healthy, non-demented, older individuals with cognitive decline. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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15 pages, 1307 KiB

Open AccessFeature PaperArticle

Changes in Phospholipid Composition of the Human Cerebellum and Motor Cortex during Normal Ageing

by Sarah E. Hancock, Michael G. Friedrich, Todd W. Mitchell, Roger J. W. Truscott and Paul L. Else

Nutrients 2022, 14(12), 2495; https://doi.org/10.3390/nu14122495 - 16 Jun 2022

Cited by 5 | Viewed by 2456

Abstract

(1) Background: Changes in phospholipid (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, i.e., PC, PE and PS) composition with age in the mitochondrial and microsomal membranes of the human cerebellum and motor cortex were examined and compared to previous analyses of the prefrontal cortex, hippocampus and entorhinal cortex. (2) Methods: Nano-electrospray ionization on a hybrid triple quadrupole–linear ion trap mass spectrometer was used to analyse the brain regions of subjects aged 18–104 years. (3) Results: With age, the cerebellum showed many changes in the major phospholipids (>10% of the phospholipid class). In both membrane types, these included increases in PE 18:0_22:6 and PS 18:0_22:6, decreases in PE 18:0_20:4 and PS 18:0_18:1 and an increase in PC 16:0_16:0 (microsomal membrane only). In addition, twenty-one minor phospholipids also changed. In the motor cortex, only ten minor phospholipids changed with age. With age, the acyl composition of the membranes in the cerebellum increased in docosahexaenoic acid (22:6) and decreased in the arachidonic (20:4) and adrenic (22:4) acids. A comparison of phospholipid changes in the cerebellum, motor cortex and other brain areas is provided. (4) Conclusions: The cerebellum is exceptional in the large number of major phospholipids that undergo changes (with consequential changes in acyl composition) with age, whereas the motor cortex is highly resistant to change. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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20 pages, 4782 KiB

Open AccessArticle

Phospholipid Profiles Are Selectively Altered in the Putamen and White Frontal Cortex of Huntington’s Disease

by Gabrielle R. Phillips, Sarah E. Hancock, Andrew M. Jenner, Catriona McLean, Kelly A. Newell and Todd W. Mitchell

Nutrients 2022, 14(10), 2086; https://doi.org/10.3390/nu14102086 - 16 May 2022

Cited by 5 | Viewed by 2634

Abstract

Huntington’s disease (HD) is a genetic, neurodegenerative illness that onsets in late adulthood as a series of progressive and terminal cognitive, motor, and psychiatric deficits. The disease is caused by a polyQ mutation in the Huntingtin gene (HTT), producing a polyglutamine expansion in the Huntingtin protein (HTT). HTT interacts with phospholipids in vitro; however, its interactions are changed when the protein is mutated in HD. Emerging evidence suggests that the susceptibility of brain regions to pathological stimuli is influenced by lipid composition. This study aimed to identify where and how phospholipids are changed in human HD brain tissue. Phospholipids were extracted using a modified MTBE method from the post-mortem brain of 13 advanced-stage HD patients and 13 age- and sex-matched controls. Targeted precursor ion scanning mass spectrometry was used to detect phospholipid species. In the white cortex of HD patients, there was a significantly lower abundance of phosphatidylcholine (PC) and phosphatidylserine (PS), but no difference in phosphatidylethanolamine (PE). In HD putamen, ester-linked 22:6 was lower in all phospholipid classes promoting a decrease in the relative abundance of ester polyunsaturated fatty acids in PE. No differences in phospholipid composition were identified in the caudate, grey cortex or cerebellum. Ether-linked PE fatty acids appear protected in the HD brain, as no changes were identified. The nature of phospholipid alterations in the HD brain is dependent on the lipid (subclass, species, and bond type) and the location. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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11 pages, 5227 KiB

Open AccessArticle

N-3 Polyunsaturated Fatty Acids Ameliorate Neurobehavioral Outcomes Post-Mild Traumatic Brain Injury in the Fat-1 Mouse Model

by Jessica-Dominique Lecques, Brynna J. K. Kerr, Lyn M. Hillyer, Jing X. Kang, Lindsay E. Robinson and David W. L. Ma

Nutrients 2021, 13(11), 4092; https://doi.org/10.3390/nu13114092 - 15 Nov 2021

Cited by 5 | Viewed by 2657

Abstract

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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Review

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30 pages, 847 KiB

Open AccessReview

Nutritional Quality Implications: Exploring the Impact of a Fatty Acid-Rich Diet on Central Nervous System Development

by Katarzyna Smolińska, Aleksandra Szopa, Jan Sobczyński, Anna Serefko and Piotr Dobrowolski

Nutrients 2024, 16(7), 1093; https://doi.org/10.3390/nu16071093 - 8 Apr 2024

Cited by 1 | Viewed by 3875

Abstract

Given the comprehensive examination of the role of fatty acid-rich diets in central nervous system development in children, this study bridges significant gaps in the understanding of dietary effects on neurodevelopment. It delves into the essential functions of fatty acids in neurodevelopment, including their contributions to neuronal membrane formation, neuroinflammatory modulation, neurogenesis, and synaptic plasticity. Despite the acknowledged importance of these nutrients, this review reveals a lack of comprehensive synthesis in current research, particularly regarding the broader spectrum of fatty acids and their optimal levels throughout childhood. By consolidating the existing knowledge and highlighting critical research gaps, such as the effects of fatty acid metabolism on neurodevelopmental disorders and the need for age-specific dietary guidelines, this study sets a foundation for future studies. This underscores the potential of nutritional strategies to significantly influence neurodevelopmental trajectories, advocating an enriched academic and clinical understanding that can inform dietary recommendations and interventions aimed at optimizing neurological health from infancy. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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17 pages, 1084 KiB

Open AccessReview

Effects of Omega-3 Polyunsaturated Fatty Acids Intake on Vasomotor Symptoms, Sleep Quality and Depression in Postmenopausal Women: A Systematic Review

by Ayesha Zafar Iqbal, Suet-Kei Wu, Halliru Zailani, Wei-Che Chiu, Wen-Chun Liu, Kuan-Pin Su and Shin-Da Lee

Nutrients 2023, 15(19), 4231; https://doi.org/10.3390/nu15194231 - 30 Sep 2023

Cited by 6 | Viewed by 5154

Abstract

The menopausal transition is often accompanied with distressing manifestations, such as vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of n-3 PUFAs supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic literature search of randomized controlled trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 identified studies, nine studies met the inclusion criteria and were incorporated into this systematic review. Notably, four studies detected potential benefits of n-3 PUFAs in improving hot flashes and night sweats. On the contrary, sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales, such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, we found inconclusive evidence of n-3 PUFA’s impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of n-3 PUFAs in improving vasomotor symptoms, sleep quality, and depression. Further well-designed randomized clinical trials with larger participant groups are crucial to validate and generalize these results. Review Registration: PROSPERO registration no: CRD42023421922. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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22 pages, 930 KiB

Open AccessReview

What Is the Evidence for Dietary-Induced DHA Deficiency in Human Brains?

by Andrew J. Sinclair, Yonghua Wang and Duo Li

Nutrients 2023, 15(1), 161; https://doi.org/10.3390/nu15010161 - 29 Dec 2022

Cited by 6 | Viewed by 4343

Abstract

Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by endogenous synthesis from α-linolenic acid (ALA), an essential fatty acid. Low blood levels of DHA in some westernised populations have led to speculations that child development disorders and various neurological conditions are associated with sub-optimal neural DHA levels, a proposition which has been supported by the supplement industry. This review searched for evidence of deficiency of DHA in human populations, based on elevated levels of the biochemical marker of n-3 deficiency, docosapentaenoic acid (22:5n-6). Three scenarios/situations were identified for the insufficient supply of DHA, namely in the brain of new-born infants fed with high-linoleic acid (LA), low-ALA formulas, in cord blood of women at birth who were vegetarians and in the milk of women from North Sudan. Twenty post-mortem brain studies from the developed world from adults with various neurological disorders revealed no evidence of raised levels of 22:5n-6, even in the samples with reduced DHA levels compared with control subjects. Human populations most likely at risk of n-3 deficiency are new-born and weanling infants, children and adolescents in areas of dryland agriculture, in famines, or are refugees, however, these populations have rarely been studied. This is an important topic for future research. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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11 pages, 608 KiB

Open AccessReview

Esterification of Docosahexaenoic Acid Enhances Its Transport to the Brain and Its Potential Therapeutic Use in Brain Diseases

by Amanda Lo Van, Nathalie Bernoud-Hubac and Michel Lagarde

Nutrients 2022, 14(21), 4550; https://doi.org/10.3390/nu14214550 - 28 Oct 2022

Cited by 5 | Viewed by 3005

Abstract

Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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33 pages, 2070 KiB

Open AccessReview

Fatty Acids: A Safe Tool for Improving Neurodevelopmental Alterations in Down Syndrome?

by Carmen Martínez-Cué and Renata Bartesaghi

Nutrients 2022, 14(14), 2880; https://doi.org/10.3390/nu14142880 - 13 Jul 2022

Cited by 5 | Viewed by 3107

Abstract

The triplication of chromosome 21 causes Down syndrome (DS), a genetic disorder that is characterized by intellectual disability (ID). The causes of ID start in utero, leading to impairments in neurogenesis, and continue into infancy, leading to impairments in dendritogenesis, spinogenesis, and connectivity. These defects are associated with alterations in mitochondrial and metabolic functions and precocious aging, leading to the early development of Alzheimer’s disease. Intense efforts are currently underway, taking advantage of DS mouse models to discover pharmacotherapies for the neurodevelopmental and cognitive deficits of DS. Many treatments that proved effective in mouse models may raise safety concerns over human use, especially at early life stages. Accumulating evidence shows that fatty acids, which are nutrients present in normal diets, exert numerous positive effects on the brain. Here, we review (i) the knowledge obtained from animal models regarding the effects of fatty acids on the brain, by focusing on alterations that are particularly prominent in DS, and (ii) the progress recently made in a DS mouse model, suggesting that fatty acids may indeed represent a useful treatment for DS. This scenario should prompt the scientific community to further explore the potential benefit of fatty acids for people with DS. Full article

(This article belongs to the Special Issue Update on Fatty Acids and the Brain)

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