PMID- 36769295
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230214
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Feb 3
TI  - Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and 
      Calu-3 Cells.
LID - 10.3390/ijms24032972 [doi]
LID - 2972
AB  - 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 
      (PPARalpha), 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.
FAU - Bachmann, Cornel Manuel
AU  - Bachmann CM
AD  - Experimental Neurology, Saarland University, 66421 Homburg, Germany.
FAU - Janitschke, Daniel
AU  - Janitschke D
AUID- ORCID: 0000-0001-8966-0184
AD  - Experimental Neurology, Saarland University, 66421 Homburg, Germany.
FAU - Lauer, Anna Andrea
AU  - Lauer AA
AUID- ORCID: 0000-0002-8327-452X
AD  - Experimental Neurology, Saarland University, 66421 Homburg, Germany.
AD  - Nutrition Therapy and Counseling, Campus Rheinland, SRH University of Applied 
      Health Sciences, 51377 Leverkusen, Germany.
FAU - Erhardt, Tobias
AU  - Erhardt T
AD  - Physical Therapy, Campus Karlsruhe, SRH University of Applied Health Sciences, 
      76185 Karlsruhe, Germany.
FAU - Hartmann, Tobias
AU  - Hartmann T
AUID- ORCID: 0000-0001-7481-6430
AD  - Experimental Neurology, Saarland University, 66421 Homburg, Germany.
AD  - Deutsches Institut fur DemenzPravention (DIDP), Saarland University, 66421 
      Homburg, Germany.
FAU - Grimm, Marcus Otto Walter
AU  - Grimm MOW
AUID- ORCID: 0000-0002-4160-6506
AD  - Experimental Neurology, Saarland University, 66421 Homburg, Germany.
AD  - Nutrition Therapy and Counseling, Campus Rheinland, SRH University of Applied 
      Health Sciences, 51377 Leverkusen, Germany.
AD  - Deutsches Institut fur DemenzPravention (DIDP), Saarland University, 66421 
      Homburg, Germany.
FAU - Grimm, Heike Sabine
AU  - Grimm HS
AD  - Experimental Neurology, Saarland University, 66421 Homburg, Germany.
AD  - Nutrition Therapy and Counseling, Campus Rheinland, SRH University of Applied 
      Health Sciences, 51377 Leverkusen, Germany.
LA  - eng
GR  - 01ED1509/the EU Joint Programme - Neurodegenerative Disease Research (JPND) and 
      BMBF grants MIND-AD/
GR  - 211696/European Commission under the frame-work programme of the European Union, 
      LipiDiDiet/
GR  - 01ED2003/EURO-FINGERS/
PT  - Journal Article
DEP - 20230203
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - Q8X02027X3 (Gemfibrozil)
RN  - 0 (Triglycerides)
RN  - 0 (Fatty Acids)
RN  - 0 (Hypolipidemic Agents)
SB  - IM
MH  - Humans
MH  - Gemfibrozil/pharmacology
MH  - *Alzheimer Disease/drug therapy
MH  - *Neuroblastoma/drug therapy
MH  - Triglycerides/metabolism
MH  - Fatty Acids
MH  - Hypolipidemic Agents/pharmacology/therapeutic use
PMC - PMC9917468
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - carnitines
OT  - gemfibrozil
OT  - lipid droplets
OT  - lipidomics
OT  - lung diseases
OT  - lyso-phosphatidylcholine
OT  - phosphatidylcholine
OT  - plasmalogens
OT  - renal diseases
OT  - triglycerides
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/15 06:00
PMCR- 2023/02/03
CRDT- 2023/02/11 01:25
PHST- 2022/12/28 00:00 [received]
PHST- 2023/01/27 00:00 [revised]
PHST- 2023/01/30 00:00 [accepted]
PHST- 2023/02/11 01:25 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/02/03 00:00 [pmc-release]
AID - ijms24032972 [pii]
AID - ijms-24-02972 [pii]
AID - 10.3390/ijms24032972 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Feb 3;24(3):2972. doi: 10.3390/ijms24032972.