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  Characterization of Lipid and Lipid Droplet Metabolism in Human HCC

Berndt, N., Eckstein, J., Heucke, N., Gajowski, R., Stockmann, M., Meierhofer, D., et al. (2019). Characterization of Lipid and Lipid Droplet Metabolism in Human HCC. Cells, 8(5): 512. doi:10.3390/cells8050512.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-AEE7-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-AEE8-4
Genre: Journal Article

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Berndt et al_2019.pdf (Publisher version), 2MB
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© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

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 Creators:
Berndt , Nikolaus , Author
Eckstein, Johannes , Author
Heucke, Niklas , Author
Gajowski, Robert1, Author              
Stockmann, Martin , Author
Meierhofer, David1, Author              
Holzhütter, Hermann-Georg , Author
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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Free keywords: tumor metabolism; lipid droplet metabolism; mathematical model; kinetic modeling; liver; hepatocellular carcinoma
 Abstract: Human hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with cirrhosis. While previous metabolic studies of HCC have mainly focused on the glucose metabolism (Warburg effect), less attention has been paid to tumor-specific features of the lipid metabolism. Here, we applied a computational approach to analyze major pathways of fatty acid utilization in individual HCC. To this end, we used protein intensity profiles of eleven human HCCs to parameterize tumor-specific kinetic models of cellular lipid metabolism including formation, enlargement, and degradation of lipid droplets (LDs). Our analysis reveals significant inter-tumor differences in the lipid metabolism. The majority of HCCs show a reduced uptake of fatty acids and decreased rate of β-oxidation, however, some HCCs display a completely different metabolic phenotype characterized by high rates of β-oxidation. Despite reduced fatty acid uptake in the majority of HCCs, the content of triacylglycerol is significantly enlarged compared to the tumor-adjacent tissue. This is due to tumor-specific expression profiles of regulatory proteins decorating the surface of LDs and controlling their turnover. Our simulations suggest that HCCs characterized by a very high content of triglycerides comprise regulatory peculiarities that render them susceptible to selective drug targeting without affecting healthy tissue.

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Language(s): eng - English
 Dates: 2019-05-212019-05-27
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.3390/cells8050512
 Degree: -

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Title: Cells
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MPDI (Multidisciplinary Digital Publishing Institute)
Pages: 18 Volume / Issue: 8 (5) Sequence Number: 512 Start / End Page: - Identifier: ISSN: 2073-4409