Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells

Autor: Cornel Manuel Bachmann, Daniel Janitschke, Anna Andrea Lauer, Tobias Erhardt, Tobias Hartmann, Marcus Otto Walter Grimm, Heike Sabine Grimm
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 3, p 2972 (2023)
Druh dokumentu: article
ISSN: 24032972
1422-0067
1661-6596
DOI: 10.3390/ijms24032972
Popis: Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood. As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in many tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism. However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many diseases, such as Alzheimer’s disease, cancer, fatty liver disease and type-2 diabetes, treatment with gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase in intracellular triglycerides (SH-SY5Y: 170.3%; HEK: 272.1%; Calu-3: 448.1%), suggesting that the decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which could be important in diseases, such as Alzheimer’s disease.
Databáze: Directory of Open Access Journals
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