Remodeling of lipid bodies by docosahexaenoic acid in activated microglial cells
Open accessAbstract
BACKGROUND: Organelle remodeling processes are evolutionarily conserved and involved in cell functions during development, aging, and cell death. Some endogenous and exogenous molecules can modulate these processes. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, has mainly been considered as a modulator of plasma membrane fluidity in brain development and aging, while DHA's role in organelle remodeling in specific neural cell types at the ultrastructural level remains largely unexplored. DHA is notably incorporated into dynamic organelles named lipid bodies (LBs). We hypothesized that DHA could attenuate the inflammatory response in lipopolysaccharide (LPS)-activated microglia by remodeling LBs and altering their functional interplay with mitochondria and other associated organelles. RESULTS: We used electron microscopy to analyze at high spatial resolution organelle changes in N9 microglial cells exposed to the proinflammogen LPS, with or without DHA supplementation. Our results revealed that DHA reverses several effects of LPS in organelles. In particular, a large number of very small and grouped LBs was exclusively found in microglial cells exposed to DHA. In contrast, LBs in LPS-stimulated cells in the absence of DHA were sparse and large. LBs formed in the presence of DHA were generally electron-dense, suggesting DHA incorporation into these organelles. The accumulation of LBs in microglial cells from mouse and human was confirmed in situ. In addition, DHA induced numerous contacts between LBs and mitochondria and reversed the frequent disruption of mitochondrial integrity observed upon LPS stimulation. Dilation of the endoplasmic reticulum lumen was also infrequent following DHA treatment, suggesting that DHA reduces oxidative stress and protein misfolding. Lipidomic analysis in N9 microglial cells treated with DHA revealed an increase in phosphatidylserine, indicating the role of this phospholipid in normalization and maintenance of physiological membrane functions. This finding was supported by a marked reduction of microglial filopodia and endosome number and significant reduction of LPS-induced phagocytosis. CONCLUSIONS: DHA attenuates the inflammatory response in LPS-stimulated microglial cells by remodeling LBs and altering their interplay with mitochondria and other associated organelles. Our findings point towards a mechanism by which omega-3 DHA participates in organelle reorganization and contributes to the maintenance of neural cell homeostasis.
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Inflammatory triggers like lipopolysaccharide, fatty acids, and aging promote lipid droplet accumulation in primary microglial cells and cell lines.
“Inflammatory triggers like lipopolysaccharide (LPS)35,19, fatty acids36, and aging20 promote LD accumulation in primary microglial cells and cell lines.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [19]
The Results (Remodeling of lipid bodies; page unavailable) show that LPS increased lipid vacuoles in the N9 microglial cell line, but distinguish those vacuoles from lipid droplets, which were rare under both control and LPS-only conditions. This source therefore supports LPS-related lipid-body accumulation, not the more specific claim that LPS alone promotes lipid-droplet accumulation. The sentence assigns fatty acids and aging to other citations. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLPS-mediated inflammation promotes lipid droplet accumulation in immune cells.
“LPS mediated-inflammation is known to promote LD accumulation in immune cells [19,69,70].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [70]
The Results section (page unavailable) reports that LPS increased lipid vacuoles in N9 microglial cells, which are immune cells. But it distinguishes vacuoles from droplets: droplets were rare with LPS alone and accumulated with DHA treatment. The source therefore supports increased lipid bodies under LPS, not the specific claim of lipid droplet accumulation. (LLM, conf=0.88)
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 [19]
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- Authors
- Tremblay, M.-E., Zhang, I., Bisht, K., Savage, J. C., Lecours, C., Parent, M., Titorenko, V., & Maysinger, D.
- Affiliations
- McGill University (CA)
- Université Laval (CA)
- Institut Universitaire en Santé Mentale de Québec (CA)
- Concordia University (CA)
- Venue
- Journal of Neuroinflammation
- Published
- 2016-05-24
- Volume
- 13
- Issue
- 1
- Pages
- 116-116
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC4879742
- OpenAlex
- W2396651792
- Cited by
- 66
- References
- 92
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 16 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 3
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-05308, RGPIN-2015-04994)
- Institute of Aging (MOP 119425)
- Scottish Rite Charitable Foundation of Canada
- The Banting Research Foundation
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- docosahexaenoic acid, omega-3 polyunsaturated fatty acids, lipid droplets, microglia, lipopolysaccharide, neuroinflammation, mitochondrial integrity, organelle remodeling, phosphatidylserine, endoplasmic reticulum, phagocytosis, filopodia, N9 cells, lipidomics, membrane fluidity
- MeSH terms
- Animals, Cell Line, Transformed, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Fatty Acids, Lipopolysaccharides, Phagocytosis, Time Factors, Triglycerides, Organelles, Cytokines, Microglia, Microscopy, Electron, Transmission, Mice, Lipid Droplets
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