Palmitic acid increasing the entry of lipopolysaccharide into microglial cytosol and eliciting pyroptosis and apoptosis

doi:10.16098/j.issn.0529-1356.2025.04.004

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (4) : 404-412. DOI: 10.16098/j.issn.0529-1356.2025.04.004

Palmitic acid increasing the entry of lipopolysaccharide into microglial cytosol and eliciting pyroptosis and apoptosis

FENG Yu-hu1 YANG Yan-zhuo¹ Lü Hai-yan² YU Qing-ting¹ YANG Zui-su¹ YUAN Fa-lei^1*

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Abstract

Objective To investigate the types and mechanisms of microglial cell death induced by interaction between palmitic acid (PA) and lipopolysaccharide (LPS). Methods BV-2 microglial cells were divided into three groups for apoptosis research, BSA group, PA treatment group, and staurosporine (STA) group. They were further divided into four groups for necrosis research, BSA group, BSA + inhibitor group, PA group, and PA + inhibitor group. Western blotting was conducted to assess the expression levels of key proteins involved in apoptosis and necrosis pathways. The effect of PA on microglial cells was validated through feeding a high-fat diet to Institute of Cancer Research(ICR) mice. Results Apoptotic microglia were observed in both BSA group and PA group, PA significantly induced the activation of caspase-3, caspase-7, and poly ADP-ribose polymerase(PARP). However, compared to the BSA group, the level of activated Caspase-7 in the STA group did not change significantly. Inhibition of ferroptosis, necroptosis, or autophagy did not protect against PA-induced cell damage, while the Caspase-11 inhibitor, wedelolactone (WE), significantly improved PA induced cell damage. This study also found that PA could promote LPS entry into microglial cells and induce pyroptosis. This phenomenon and the protective effect of WE were further confirmed in a high-fat diet mouse model through immunofluorescent staining and Western blotting. Conclusion PA induces apoptosis and pyroptosis in microglial cells, while simultaneously promoting LPS entry into microglial cells and inducing pyroptosis.

Key words

Palmitic acid / Microglia / Pyroptosis / Wedelolactone / BV-2 microglial cell / Western blotting / Mouse

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FENG Yu-hu YANG Yan-zhuo Lü Hai-yan YU Qing-ting YANG Zui-su YUAN Fa-lei. Palmitic acid increasing the entry of lipopolysaccharide into microglial cytosol and eliciting pyroptosis and apoptosis[J]. Acta Anatomica Sinica. 2025, 56(4): 404-412 https://doi.org/10.16098/j.issn.0529-1356.2025.04.004

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