Saturated fatty acids activate microglia via Toll-like receptor 4/NF-κB signalling
Open accessAbstract
Diets rich in SFA have been implicated in Alzheimer's disease (AD). There is strong evidence to suggest that microglial activation augments the progression of AD. However, it remains uncertain whether SFA can initiate microglial activation and whether this response can cause neuronal death. Using the BV-2 microglial cell line and primary microglial culture, we showed that palmitic acid (PA) and stearic acid (SA) could activate microglia, as assessed by reactive morphological changes and significantly increased secretion of pro-inflammatory cytokines, NO and reactive oxygen species, which trigger primary neuronal death. In addition, the mRNA level of these pro-inflammatory mediators determined by RT-PCR was also increased by PA and SA. We further investigated the intracellular signalling mechanism underlying the release of pro-inflammatory mediators from PA-activated microglial cells. The present results showed that PA activated the phosphorylation and nuclear translocation of the p65 subunit of NF-κB. Furthermore, pyrrolidine dithiocarbamate, a NF-κB inhibitor, attenuated the production of pro-inflammatory mediators except for IL-6 in PA-stimulated microglia. Administration of anti-Toll-like receptor (TLR)4-neutralising antibody repressed PA-induced NF-κB activation and pro-inflammatory mediator production. In conclusion, the present in vitro study demonstrates that SFA could activate microglia and stimulate the TLR4/NF-κB pathway to trigger the production of pro-inflammatory mediators, which may contribute to neuronal death.
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Altered lipid metabolism and extrinsic supplementation with various lipid substrates have a major impact on microglial reprogramming.
“Altered lipid metabolism and extrinsic supplementation with various lipid substrates both have a major impact on microglial reprogramming [60,61,62,63,64].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [64]
The Abstract (page unavailable) reports that supplementation with two saturated fatty acids, palmitic and stearic acid, activated cultured microglia and increased inflammatory mediators. The paper does not establish that altered lipid metabolism affects microglia, and its findings do not extend to lipid substrates generally. (LLM, conf=0.88)
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- Authors
- Wang, Z., Liu, D., Wang, F., Liu, S., Zhao, S., Ling, E.-A., & Hao, A.
- Affiliations
- Shandong University (CN)
- National University of Singapore (SG)
- Corresponding author
- Hao, Aijun
- Venue
- British Journal of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2011-06-29
- Volume
- 107
- Issue
- 2
- Pages
- 229-241
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2159265751
- Cited by
- 239
- References
- 6
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 23 · 2023: 22 · 2022: 24 · 2021: 29 · 2020: 22 · 2019: 28 · 2018: 10 · 2017: 11 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 7 · 2012: 3
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (973 Program, 81071057, 30771142)
- Natural Science Foundation of Shandong Province (J200823, Z2007C11, ZR2010HQ022)
- National Key Research and Development Program of China (2007CB512001, 2011CB966201)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- saturated fatty acids, microglial activation, TLR4, NF-κB signaling, palmitic acid, stearic acid, Alzheimer's disease, inflammatory cytokines, nitric oxide, reactive oxygen species, neuronal cell death, pyrrolidine dithiocarbamate
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Mice, Inbred BALB C, Nerve Tissue Proteins, Phosphorylation, Protein Processing, Post-Translational, RNA, Messenger, Stearic Acids, Signal Transduction, Up-Regulation, Cytokines, Apoptosis, Reactive Oxygen Species, Microglia, Genes, Reporter, Palmitic Acid, Protein Transport, Toll-Like Receptor 4, Mice, Transcription Factor RelA, Nitric Oxide Synthase Type II
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