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Cited by 54Fatty Acid Research and HealthNeuroinflammation and Neurodegeneration MechanismsLipid metabolism and biosynthesis

Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids

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Urso, C.J., Zhou, Heping·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22169093PMC PMC8396597
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Abstract

Obesity and metabolic syndrome are associated with cognitive decline and dementia. Palmitic acid (PA) is increased in the cerebrospinal fluid of obese patients with cognitive impairment. This study was therefore designed to examine fatty acid (FA) lipotoxicity in BV2 microglia cells. We found that PA induced time- and dose-dependent decrease in cell viability and increase in cell death without affecting the cell cycle profile and that PA lipotoxicity did not depend on cell surface free fatty acid receptors but rather on FA uptake. Treatment with sulfosuccinimidyl oleate (SSO), an irreversible inhibitor of fatty acid translocase CD36, significantly inhibited FA uptake in BSA- and PA-treated cells and blocked PA-induced decrease in cell viability. Inhibition of ER stress or treatment with N-acetylcysteine was not able to rescue PA lipotoxicity. Our study also showed that unsaturated fatty acids (UFAs), such as linoleic acid (LA), oleic acid (OA), α-linolenic acid (ALA), and docosahexaenoic acid (DHA), were not lipotoxic but instead protected microglia against PA-induced decrease in cell viability. Co-treatment of PA with LA, OA, and DHA significantly inhibited FA uptake in PA-treated cells. All UFAs tested induced the incorporation of FAs into and the amount of neutral lipids, while PA did not significantly affect the amount of neutral lipids compared with BSA control.

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  • Metabolites such as lipid, free fatty acid, and glucose are capable of stimulating microglia and metabolic reprogramming has inherent linkage with microglial activation.

    “Recently, acuumulating evidence show that metabolites such as lipid, free fatty acid, and glucose are capable of stimulating microglia and metabolic reprogramming has inherent linkage with microglial activation (immunobolism) [17–20].”

    From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [19]

    The Introduction (page not provided) says fatty acids may affect microglial function and that studies have examined their effects on microglial immune activation. It does not establish that glucose stimulates microglia. The Discussion (page not provided) says the relationship between microglial metabolic pathways and immune regulation remains to be examined, rather than establishing a link between metabolic reprogramming and activation. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • 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 [36]

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Sorted by citations

Authors
Urso, C. J., & Zhou, H.
Affiliations
Seton Hall University (US)
Corresponding author
Zhou, Heping
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-08-23
Volume
22
Issue
16
Pages
9093
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22169093
PMC
PMC8396597
OpenAlex
W3194902043
Cited by
54
References
6
Citations by year
2026: 11 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 8 · 2021: 1
FWCI
5.26
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
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
palmitic acid, lipotoxicity, microglia, unsaturated fatty acids, fatty acid uptake, CD36, linoleic acid, oleic acid, alpha-linolenic acid, docosahexaenoic acid, neuroinflammation, obesity, metabolic syndrome, cognitive decline, endoplasmic reticulum stress, neutral lipids
MeSH terms
Animals, Cell Survival, Fatty Acids, Nonesterified, Fatty Acids, Unsaturated, Lipids, Cell Death, Microglia, Palmitic Acid, Mice

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