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

Department of Biological Sciences, Seton Hall University, South Orange, NJ 07079, USA
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Author to whom correspondence should be addressed.
Academic Editor: Georg R. Zoidl
Int. J. Mol. Sci. 2021, 22(16), 9093; https://doi.org/10.3390/ijms22169093
Received: 24 June 2021 / Revised: 16 August 2021 / Accepted: 20 August 2021 / Published: 23 August 2021
(This article belongs to the Section Molecular Neurobiology)
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. View Full-Text
Keywords: fatty acid uptake; lipid droplets; lipoprotection; lipotoxicity; neutral lipid accumulation; palmitic acid; unsaturated fatty acids fatty acid uptake; lipid droplets; lipoprotection; lipotoxicity; neutral lipid accumulation; palmitic acid; unsaturated fatty acids
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MDPI and ACS Style

Urso, C.J.; Zhou, H. Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids. Int. J. Mol. Sci. 2021, 22, 9093. https://doi.org/10.3390/ijms22169093

AMA Style

Urso CJ, Zhou H. Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids. International Journal of Molecular Sciences. 2021; 22(16):9093. https://doi.org/10.3390/ijms22169093

Chicago/Turabian Style

Urso, C.J., and Heping Zhou. 2021. "Palmitic Acid Lipotoxicity in Microglia Cells Is Ameliorated by Unsaturated Fatty Acids" International Journal of Molecular Sciences 22, no. 16: 9093. https://doi.org/10.3390/ijms22169093

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