Direct and indirect effects of lipids on microglia function
Open accessAbstract
Microglia are key players in brain function by maintaining brain homeostasis across lifetime. They participate to brain development and maturation through their ability to release neurotrophic factors, to remove immature synapses or unnecessary neural progenitors. They modulate neuronal activity in healthy adult brains and they also orchestrate the neuroinflammatory response in various pathophysiological contexts such as aging and neurodegenerative diseases. One of the main features of microglia is their high sensitivity to environmental factors, partly via the expression of a wide range of receptors. Recent data pinpoint that dietary fatty acids modulate microglia function. Both the quantity and the type of fatty acid are potent modulators of microglia physiology. The present review aims at dissecting the current knowledge on the direct and indirect mechanisms (focus on gut microbiota and hormones) through which fatty acids influence microglial physiology. We summarize main discoveries from in vitro and in vivo models on fatty acid-mediated microglial modulation. All these studies represent a promising field of research that could promote using nutrition as a novel therapeutic or preventive tool in diseases involving microglia dysfunctions.
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Dietary patterns affect levels and composition of circulating lipids in plasma, which affects activation of immune cells in CNS.
“Dietary patterns greatly affect the levels and composition of circulating lipids in the plasma (e.g., the ratio between saturated and unsaturated fatty acids), which also affects the activation of immune cells in the CNS.108,109”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [109]
Section 2 (p. 11) says dietary intake controls body lipid levels and that peripheral lipids may influence microglial function. The Conclusion (p. 15) says dietary lipids affect microglia directly or indirectly. The paper does not establish the more specific claim that dietary patterns change the levels and saturated-to-unsaturated composition of circulating lipids in plasma, which then changes CNS immune-cell activation. (LLM, conf=0.85)
Experimental — accuracy not yet measuredChanges in microglial lipid content can affect their state and function.
“changes in microglial lipid content can also affect their state and function18,19,20,21”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [18]
Evidence for unsaturated, mono-, and poly-unsaturated fatty acids impacting microglial function comes from both in vitro and in vivo studies.
“Evidence for unsaturated, mono-, and poly-unsaturated fatty acids impacting microglial function comes from both in vitro and in vivo studies [70].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [70]
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References 224 · Cited by 50
- Authors
- Leyrolle, Q., Layé, S., & Nadjar, A.
- Affiliations
- Université de Bordeaux (FR)
- Corresponding author
- Nadjar, A.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 708
- Pages
- 134348
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2951171425
- Cited by
- 50
- References
- 224
- Citations by year
- 2026: 1 · 2025: 12 · 2024: 7 · 2023: 14 · 2022: 2 · 2021: 10 · 2020: 3 · 2019: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuroscience Letters (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Funders
- Institut National pour la Recherche Agronomique
- Bordeaux University
- Foundation for Medical research
- French Foundation
- Excellence Initiative Labex Brain and the Nouvelle Région Aquitaine
- region Ile de France (PICRI
- Ceberal Palsy Foundation) and by the FRM
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- microglia, dietary fatty acids, lipid signaling, gut microbiota, hormones, neuroinflammation, brain development, brain homeostasis, neurodegenerative diseases, aging
- MeSH terms
- Gastrointestinal Microbiome, Animals, Fatty Acids, Hormones, Humans, Microglia, Lipid Metabolism
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