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Gindlhuber, J; Schinagl, M; Liesinger, L; Darnhofer, B; Tomin, T; Schittmayer, M; Birner-Gruenberger, R.
Hepatocyte Proteome Alterations Induced by Individual and Combinations of Common Free Fatty Acids.
Int J Mol Sci. 2022; 23(6): Doi: 10.3390/ijms23063356 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Birner-Grünberger Ruth
Gindlhuber Jürgen
Co-Autor*innen der Med Uni Graz
Darnhofer Barbara
Liesinger Laura
Schinagl Maximilian
Schittmayer-Schantl Matthias
Tomin Tamara
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Abstract:
Non-alcoholic fatty liver disease is a pathology with a hard-to-detect onset and is estimated to be present in a quarter of the adult human population. To improve our understanding of the development of non-alcoholic fatty liver disease, we treated a human hepatoma cell line model, HepG2, with increasing concentrations of common fatty acids, namely myristic, palmitic and oleic acid. To reproduce more physiologically representative conditions, we also included combinations of these fatty acids and monitored the cellular response with an in-depth proteomics approach and imaging techniques. The two saturated fatty acids initially presented a similar phenotype of a dose-dependent decrease in growth rates and impaired lipid droplet formation. Detailed analysis revealed that the drop in the growth rates was due to delayed cell-cycle progression following myristic acid treatment, whereas palmitic acid led to cellular apoptosis. In contrast, oleic acid, as well as saturated fatty acid mixtures with oleic acid, led to a dose-dependent increase in lipid droplet volume without adverse impacts on cell growth. Comparing the effects of harmful single-fatty-acid treatments and the well-tolerated fatty acid mixes on the cellular proteome, we were able to differentiate between fatty-acid-specific cellular responses and likely common lipotoxic denominators.
Find related publications in this database (using NLM MeSH Indexing)
Fatty Acids - metabolism
Fatty Acids, Nonesterified - metabolism, pharmacology
Hepatocytes - metabolism
Humans - administration & dosage
Non-alcoholic Fatty Liver Disease - metabolism
Oleic Acid - metabolism, pharmacology
Palmitic Acid - metabolism, pharmacology
Proteome - metabolism

Find related publications in this database (Keywords)
NAFLD
lipotoxicity
myristic acid
palmitic acid
oleic acid
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