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

Author:

Bachmann Cornel Manuel1,Janitschke Daniel1ORCID,Lauer Anna Andrea12ORCID,Erhardt Tobias3,Hartmann Tobias14ORCID,Grimm Marcus Otto Walter124ORCID,Grimm Heike Sabine12

Affiliation:

1. Experimental Neurology, Saarland University, 66421 Homburg, Germany

2. Nutrition Therapy and Counseling, Campus Rheinland, SRH University of Applied Health Sciences, 51377 Leverkusen, Germany

3. Physical Therapy, Campus Karlsruhe, SRH University of Applied Health Sciences, 76185 Karlsruhe, Germany

4. Deutsches Institut für DemenzPrävention (DIDP), Saarland University, 66421 Homburg, Germany

Abstract

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.

Funder

European Union

EU Joint Programme–Neurodegenerative Disease Research (JPND) and BMBF grants MIND-AD

EURO-FINGERS

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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