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Effect of Toxicants on Fatty Acid Metabolism in HepG2 Cells

Overview of attention for article published in Frontiers in Pharmacology, April 2018
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Title
Effect of Toxicants on Fatty Acid Metabolism in HepG2 Cells
Published in
Frontiers in Pharmacology, April 2018
DOI 10.3389/fphar.2018.00257
Pubmed ID
Authors

David Grünig, Urs Duthaler, Stephan Krähenbühl

Abstract

Impairment of hepatic fatty acid metabolism can lead to liver steatosis and injury. Testing drugs for interference with hepatic fatty acid metabolism is therefore important. To find out whether HepG2 cells are suitable for this purpose, we investigated the effect of three established fatty acid metabolism inhibitors and of three test compounds on triglyceride accumulation, palmitate metabolism, the acylcarnitine pool and dicarboxylic acid accumulation in the cell supernatant and on ApoB-100 excretion in HepG2 cells. The three established inhibitors [etomoxir, methylenecyclopropylacetic acid (MCPA), and 4-bromocrotonic acid (4-BCA)] depleted mitochondrial ATP at lower concentrations than cytotoxicity occurred, suggesting mitochondrial toxicity. They inhibited palmitate metabolism at similar or lower concentrations than ATP depletion, and 4-BCA was associated with cellular fat accumulation. They caused specific changes in the acylcarnitine pattern and etomoxir an increase of thapsic (C18 dicarboxylic) acid in the cell supernatant, and did not interfere with ApoB-100 excretion (marker of VLDL export). The three test compounds (amiodarone, tamoxifen, and the cannabinoid WIN 55,212-2) depleted the cellular ATP content at lower concentrations than cytotoxicity occurred. They all caused cellular fat accumulation and inhibited palmitate metabolism at similar or higher concentrations than ATP depletion. They suppressed medium-chain acylcarnitines in the cell supernatant and amiodarone and tamoxifen impaired thapsic acid production. Tamoxifen and WIN 55,212-2 decreased cellular ApoB-100 excretion. In conclusion, the established inhibitors of fatty acid metabolism caused the expected effects in HepG2 cells. HepG cells proved to be useful for the detection of drug-associated toxicities on hepatocellular fatty acid metabolism.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 21%
Student > Bachelor 5 12%
Researcher 4 9%
Student > Master 4 9%
Student > Doctoral Student 2 5%
Other 2 5%
Unknown 17 40%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 6 14%
Biochemistry, Genetics and Molecular Biology 6 14%
Agricultural and Biological Sciences 4 9%
Environmental Science 2 5%
Chemistry 2 5%
Other 5 12%
Unknown 18 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2018.
All research outputs
#18,604,390
of 23,045,021 outputs
Outputs from Frontiers in Pharmacology
#8,403
of 16,374 outputs
Outputs of similar age
#253,360
of 326,560 outputs
Outputs of similar age from Frontiers in Pharmacology
#189
of 398 outputs
Altmetric has tracked 23,045,021 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,374 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 326,560 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 398 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.