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Cited by 61Neuroinflammation and Neurodegeneration MechanismsFatty Acid Research and HealthImmune Response and Inflammation

Palmitic Acid and Oleic Acid Differently Modulate TLR2-Mediated Inflammatory Responses in Microglia and Macrophages

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Howe, Anne-Marie, Burke, Sinéad, O’Reilly, Marcella E., McGillicuddy, Fiona C., Costello, Derek A.·2022·Molecular Neurobiology
DOI 10.1007/s12035-022-02756-zPMC PMC9016023
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Abstract

The relationship between systemic immunity and neuroinflammation is widely recognised. Infiltration of peripheral immune cells to the CNS during certain chronic inflammatory states contributes significantly to neuropathology. Obesity and its co-morbidities are primary risk factors for neuroinflammatory and neurodegenerative conditions, including Alzheimer’s disease (AD). Dietary fats are among the most proinflammatory components of the obesogenic diet and play a prominent role in the low-grade systemic inflammation associated with the obese state. Saturated fatty acid (SFA) is largely implicated in the negative consequences of obesity, while the health benefits of monounsaturated fatty acid (MUFA) are widely acknowledged. The current study sought to explore whether SFA and MUFA differently modulate inflammatory responses in the brain, compared with peripheral immune cells. Moreover, we assessed the neuroinflammatory impact of high-fat-induced obesity and hypothesised that a MUFA-rich diet might mitigate inflammation despite obesogenic conditions. Toll-like receptor (TLR)2 mediates the inflammation associated with both obesity and AD. Using the TLR2 agonist lipoteichoic acid (LTA), we report that pre-exposure to either palmitic acid (PA) or oleic acid (OA) attenuated cytokine secretion from microglia, but heightened sensitivity to nitric oxide (NO) production. The reduction in cytokine secretion was mirrored in LTA-stimulated macrophages following exposure to PA only, while effects on NO were restricted to OA, highlighting important cell-specific differences. An obesogenic diet over 12 weeks did not induce prominent inflammatory changes in either cortex or hippocampus, irrespective of fat composition. However, we reveal a clear disparity in the effects of MUFA under obesogenic and non-obesogenic conditions.

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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 [108]

    The Introduction reports that postprandial lipoproteins following a monounsaturated-fat-rich meal can bias microglia toward an anti-inflammatory phenotype, and the Discussion says fatty-acid exposure may alter microglial responses to an inflammatory challenge. But the paper does not establish that dietary patterns change the levels or saturated-to-unsaturated composition of circulating plasma lipids as the proposed route to CNS immune-cell activation. The Discussion also reports no robust microglial activation after the study’s 12-week high-fat diets. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Howe, A.-M., Burke, S., O’Reilly, M. E., McGillicuddy, F. C., & Costello, D. A.
Affiliations
University College Dublin (IE)
Corresponding author
Costello, Derek A.
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2022-01-25
Volume
59
Issue
4
Pages
2348-2362
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-022-02756-z
PMC
PMC9016023
OpenAlex
W4207044541
Cited by
61
References
15
Citations by year
2026: 9 · 2025: 16 · 2024: 17 · 2023: 16 · 2022: 3
FWCI
4.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurobiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust (097311/Z/11/Z)
  • UCD School of Biomolecular & Biomedical Science (Graduate Research Scholarship)
  • University College Dublin
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
palmitic acid, oleic acid, saturated fatty acids, monounsaturated fatty acids, TLR2, lipoteichoic acid, neuroinflammation, microglia, macrophages, nitric oxide, cytokine production, high-fat diet, obesity, Alzheimer's disease, obesogenic diet, dietary fat
MeSH terms
Dietary Fats, Fatty Acids, Fatty Acids, Monounsaturated, Humans, Inflammation, Macrophages, Nitric Oxide, Obesity, Cytokines, Microglia, Oleic Acid, Palmitic Acid, Toll-Like Receptor 2

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