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Lipopolysaccharide Stimulates Triglyceride Accumulation and Lipid Droplet Biogenesis in PC12 Cells: the Role of Carnitine Palmitoyltransferase 1 Down-Regulation and Suppression of Fatty Acid Oxidation

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Abstract

Inflammation and oxidative stress are well known to induce the biogenesis of lipid droplets (LDs) in various cell types, in which fatty acids are deposited as components of triglycerides (TGs) and/or cholesterol esters. This metabolic shift is critical for cell protection against the toxicity of excess lipids or their oxidative derivatives produced under various stressful exposures, including oxidative stress. The effect of bacterial lipopolysaccharide (LPS) on LD formation in CNS structures was mainly studied on microglial cells, whereas its effect on lipid metabolism in neurons, potentially associated with LD formation, has been studied neither on cell lines nor on primary neuronal cultures. This work was carried out on the PC12 neuronal cell line, which is widely used to explore the mechanisms of neuroinflammation and neurodegeneration, aiming to study the effects of LPS on LD formation, neutral lipid accumulation, and metabolism of major lipid classes, as well as to elucidate the mechanism mediating these effects. PC12 cell incubation with LPS for 24 h led to a significant accumulation of LDs and an increase in the TG level. Etomoxir, a carnitine palmitoyltransferase 1 (CPT1) inhibitor, also induced an increase in an absolute TG content. To elucidate the metabolic pathways of TG accumulation, PC12 cells were preincubated with [3H]-oleic acid and then examined for radioactive label incorporation into major lipid classes. LPS caused an increase the level of TG and free oleic acid radioactivity, accompanied by a significant inhibition of oleic acid oxidation and a decrease the radioactivity of phospholipids. PC12 cell incubation with LPS also caused a decrease in CPT1 expression. Our data indicate that in PC12 cells, LPS suppresses CPT1 expression and fatty acid oxidation, leading to sequestration of excess fatty acids into TG and the formation of LDs. Under conditions of the bacterial pathogen action, this mechanism seems to represent a cell survival strategy that protects from lipotoxicity.

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ACKNOWLEDGMENTS

The authors are grateful to associates of the Institute’s Laboratory of Molecular Endocrinology and Neurochemistry for the provision of the PC12 cell line.

Funding

This study was implemented under the state assignment to the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (no. 075-00776-19-02).

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  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    S. D. Nikolaeva, E. M. Fock & R. G. Parnova

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Contributions

Conceptualization, experimental design (R.G.P.); data collection (S.D.N., E.M.F.); data processing (S.D.N., E.M.F., R.G.P.); writing and editing the manuscript (R.G.P.).

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Correspondence to R. G. Parnova.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 7, pp. 903–916https://doi.org/10.31857/S086981392207007X.

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Nikolaeva, S.D., Fock, E.M. & Parnova, R.G. Lipopolysaccharide Stimulates Triglyceride Accumulation and Lipid Droplet Biogenesis in PC12 Cells: the Role of Carnitine Palmitoyltransferase 1 Down-Regulation and Suppression of Fatty Acid Oxidation. J Evol Biochem Phys 58, 1152–1162 (2022). https://doi.org/10.1134/S0022093022040184

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