Cited by 420Fatty Acid Research and HealthNeuroinflammation and Neurodegeneration MechanismsInflammatory mediators and NSAID effects

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Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Layé, Sophie, Nadjar, Agnès, Joffre, Corinne, Bazinet, Richard P.·2018·Pharmacological Reviews

DOI 10.1124/pr.117.014092

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Abstract

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

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“Interestingly, microglial activation leading to increased Ab phagocytosis and anti-inflammatory profile, is achieved through the use of agonists of several receptors (Yamanaka et al., 2012), in particular PPARs and retinoid X receptors, which are DHA receptors, as previously discussed.”
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Authors: Layé, S., Nadjar, A., Joffre, C., & Bazinet, R. P.
Affiliations: Université de Bordeaux (FR)
University of Toronto (CA)
ORCID: Layé, Sophie
Nadjar, Agnès
Joffre, Corinne
Bazinet, Richard P.
Venue: Pharmacological Reviews
Publisher: Elsevier BV
Published: 2018-01
Volume: 70
Issue: 1
Pages: 12-38
ISSN: 0031-6997 (ISSN-L)
DOI: 10.1124/pr.117.014092
OpenAlex: W2775574923
Cited by: 420
References: 425
Citations by year: 2026: 41 · 2025: 46 · 2024: 36 · 2023: 43 · 2022: 56 · 2021: 64 · 2020: 66 · 2019: 43 · 2018: 24
FWCI: 3.76
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Pharmacological Reviews (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
Funders: Canadian Institutes of Health Research
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords: omega-3 fatty acids, docosahexaenoic acid, polyunsaturated fatty acids, microglial activation, neuroinflammation, eicosanoids, arachidonic acid metabolites, specialized pro-resolving mediators, neurological disorders, anti-inflammatory activity, microglial phenotype
MeSH terms: Animals, Anti-Inflammatory Agents, Brain, Humans, Fatty Acids, Omega-3, Microglia

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Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

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